1  5683 147 SHORTER TELOMERE LENGTH IN PERIPHERAL BLOOD LYMPHOCYTES OF WORKERS EXPOSED TO POLYCYCLIC AROMATIC HYDROCARBONS. SHORTER TELOMERE LENGTH (TL) IN PERIPHERAL BLOOD LYMPHOCYTES (PBLS) IS PREDICTIVE OF LUNG CANCER RISK. POLYCYCLIC AROMATIC HYDROCARBONS (PAHS) ARE ESTABLISHED LUNG CARCINOGENS THAT CAUSE CHROMOSOME INSTABILITY. WHETHER PAH EXPOSURE AND ITS MOLECULAR EFFECTS ARE LINKED WITH SHORTER TL HAS NEVER BEEN EVALUATED. IN THE PRESENT STUDY, WE INVESTIGATED THE EFFECT OF CHRONIC EXPOSURE TO PAHS ON TL MEASURED IN PBLS OF POLISH MALE NON-CURRENT SMOKING COKEOVEN WORKERS AND MATCHED CONTROLS. PAH EXPOSURE AND MOLECULAR EFFECTS WERE CHARACTERIZED USING MEASURES OF INTERNAL DOSE (URINARY 1-PYRENOL), EFFECTIVE DOSE [ANTI-BENZO[A]PYRENE DIOLEPOXIDE (ANTI-BPDE)-DNA ADDUCT], GENETIC INSTABILITY (MICRONUCLEI, MN) AND DNA METHYLATION [P53 PROMOTER AND ALU AND LONG INTERSPERSED NUCLEAR ELEMENT-1 (LINE-1) REPETITIVE ELEMENTS, AS SURROGATE MEASURES OF GLOBAL METHYLATION] IN PBLS. TL WAS MEASURED BY REAL-TIME POLYMERASE CHAIN REACTION. COKEOVEN WORKERS WERE HEAVILY EXPOSED TO PAHS (79% EXCEEDED THE URINARY 1-PYRENOL BIOLOGICAL EXPOSURE INDEX) AND EXHIBITED LOWER TL (P = 0.038) THAN CONTROLS, AS WELL AS HIGHER LEVELS OF GENETIC AND CHROMOSOMAL ALTERATIONS [I.E. ANTI-BPDE-DNA ADDUCT AND MN (P < 0.0001)] AND EPIGENETIC CHANGES [I.E. P53 GENE-SPECIFIC PROMOTER AND GLOBAL METHYLATION (P <OR= 0.001)]. TL DECREASED WITH LONGER DURATION OF WORK AS COKEOVEN WORKER (P = 0.039) AND IN ALL SUBJECTS WITH HIGHER LEVELS OF ANTI-BPDE-DNA ADDUCT (P = 0.042), P53 HYPOMETHYLATION (P = 0.005) AND MN (P = 0.009). IN MULTIVARIATE ANALYSIS, YEARS OF WORK IN COKERY (P = 0.008) AND P53 HYPOMETHYLATION (P = 0.001) WERE THE PRINCIPAL DETERMINANTS OF SHORTER TL. OUR RESULTS INDICATE THAT SHORTER TL IS ASSOCIATED WITH CHRONIC PAH EXPOSURE. THE INTERRELATIONS WITH OTHER GENETIC AND EPIGENETIC MECHANISMS IN OUR DATA SUGGEST THAT SHORTER TL COULD BE A CENTRAL EVENT IN PAH CARCINOGENESIS.	2010	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
2  4378  87 MITOCHONDRIAL DNA COPY NUMBER AND EXPOSURE TO POLYCYCLIC AROMATIC HYDROCARBONS. BACKGROUND: INCREASED MITOCHONDRIAL DNA COPY NUMBER (MTDNACN) IS A BIOLOGIC RESPONSE TO MTDNA DAMAGE AND DYSFUNCTION, PREDICTIVE OF LUNG CANCER RISK. POLYCYCLIC AROMATIC HYDROCARBONS (PAHS) ARE ESTABLISHED LUNG CARCINOGENS AND MAY CAUSE MITOCHONDRIAL TOXICITY. WHETHER PAH EXPOSURE AND PAH-RELATED NUCLEAR DNA (NDNA) GENOTOXIC EFFECTS ARE LINKED WITH INCREASED MTDNACN HAS NEVER BEEN EVALUATED. METHODS: WE INVESTIGATED THE EFFECT OF CHRONIC EXPOSURE TO PAHS ON MTDNACN IN PERIPHERAL BLOOD LYMPHOCYTES (PBLS) OF 46 POLISH MALE NONCURRENT SMOKING COKE-OVEN WORKERS AND 44 MATCHED CONTROLS, WHO WERE PART OF A GROUP OF 94 STUDY INDIVIDUALS EXAMINED IN OUR PREVIOUS WORK. SUBJECTS' PAH EXPOSURE AND GENETIC ALTERATIONS WERE CHARACTERIZED THROUGH MEASURES OF INTERNAL DOSE (URINARY 1-PYRENOL), TARGET DOSE [ANTI-BENZO[A]PYRENE DIOLEPOXIDE (ANTI-BPDE)-DNA ADDUCT], GENETIC INSTABILITY (MICRONUCLEI AND TELOMERE LENGTH), AND DNA METHYLATION (P53 PROMOTER) IN PBLS. MTDNACN (MT/S) WAS MEASURED USING A VALIDATED REAL-TIME PCR METHOD. RESULTS: WORKERS WITH PAH EXPOSURE ABOVE THE MEDIAN VALUE (>3 MUMOL 1-PYRENOL/MOL CREATININE) SHOWED HIGHER MTDNACN [GEOMETRIC MEANS (GM) OF 1.06 (UNADJUSTED) AND 1.07 (AGE-ADJUSTED)] COMPARED WITH CONTROLS [GM 0.89 (UNADJUSTED); 0.89 (AGE-ADJUSTED); (P = 0.029 AND 0.016)], AS WELL AS HIGHER LEVELS OF GENETIC AND CHROMOSOMAL [I.E., ANTI-BPDE-DNA ADDUCTS (P < 0.001), MICRONUCLEI (P < 0.001), AND TELOMERE LENGTH (P = 0.053)] AND EPIGENETIC [I.E., P53 GENE-SPECIFIC PROMOTER METHYLATION (P < 0.001)] ALTERATIONS IN THE NDNA. IN THE WHOLE STUDY POPULATION, UNADJUSTED AND AGE-ADJUSTED MTDNACN WAS POSITIVELY CORRELATED WITH 1-PYRENOL (P = 0.043 AND 0.032) AND ANTI-BPDE-DNA ADDUCTS (P = 0.046 AND 0.049). CONCLUSIONS: PAH EXPOSURE AND PAH-RELATED NDNA GENOTOXICITY ARE ASSOCIATED WITH INCREASED MTDNACN. IMPACT: THE PRESENT STUDY IS SUGGESTIVE OF POTENTIAL ROLES OF MTDNACN IN PAH-INDUCED CARCINOGENESIS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
3   846  41 CHILDHOOD EXPOSURE TO AMBIENT POLYCYCLIC AROMATIC HYDROCARBONS IS LINKED TO EPIGENETIC MODIFICATIONS AND IMPAIRED SYSTEMIC IMMUNITY IN T CELLS. BACKGROUND: EVIDENCE SUGGESTS THAT EXPOSURE TO POLYCYCLIC AROMATIC HYDROCARBONS (PAHS) INCREASES ATOPY; IT IS UNCLEAR HOW PAH EXPOSURE IS LINKED TO INCREASED SEVERITY OF ATOPIC DISEASES. OBJECTIVE: WE HYPOTHESIZED THAT AMBIENT PAH EXPOSURE IS LINKED TO IMPAIRMENT OF IMMUNITY IN ATOPIC CHILDREN (DEFINED AS CHILDREN WITH ASTHMA AND/OR ALLERGIC RHINITIS) FROM FRESNO, CALIFORNIA, AN AREA WITH ELEVATED AMBIENT PAHS. METHODS: WE RECRUITED 256 SUBJECTS FROM FRESNO, CA. AMBIENT PAH CONCENTRATIONS (NG/M(3) ) WERE MEASURED USING A SPATIAL-TEMPORAL REGRESSION MODEL OVER MULTIPLE TIME PERIODS. ASTHMA DIAGNOSIS WAS DETERMINED BY CURRENT NHLBI CRITERIA. PHENOTYPING AND FUNCTIONAL IMMUNE MEASUREMENTS WERE PERFORMED FROM ISOLATED CELLS. FOR EPIGENETIC MEASUREMENTS, DNA WAS ISOLATED AND PYROSEQUENCED. RESULTS: WE SHOW THAT HIGHER AVERAGE PAH EXPOSURE WAS SIGNIFICANTLY ASSOCIATED WITH IMPAIRED TREG FUNCTION AND INCREASED METHYLATION IN THE FORKHEAD BOX PROTEIN 3 (FOXP3) LOCUS (P < 0.05), CONDITIONAL ON ATOPIC STATUS. THESE EPIGENETIC MODIFICATIONS WERE SIGNIFICANTLY LINKED TO DIFFERENTIAL PROTEIN EXPRESSION OF FOXP3 (P < 0.001). METHYLATION WAS ASSOCIATED WITH CELLULAR FUNCTIONAL CHANGES, SPECIFICALLY TREG DYSFUNCTION, AND AN INCREASE IN TOTAL PLASMA IGE LEVELS. PROTEIN EXPRESSION OF IL-10 DECREASED AND IFN-GAMMA INCREASED AS THE EXTENT OF PAH EXPOSURE INCREASED. THE STRENGTH OF THE ASSOCIATIONS GENERALLY INCREASED AS THE TIME WINDOW FOR AVERAGE PAH EXPOSURE INCREASED FROM 24 HR TO 1 YEAR, SUGGESTING MORE OF A CHRONIC RESPONSE. SIGNIFICANT ASSOCIATIONS WITH CHRONIC PAH EXPOSURE AND IMMUNE OUTCOMES WERE ALSO OBSERVED IN SUBJECTS WITH ALLERGIC RHINITIS. CONCLUSIONS AND CLINICAL RELEVANCE: COLLECTIVELY, THESE RESULTS DEMONSTRATE THAT INCREASED AMBIENT PAH EXPOSURE IS ASSOCIATED WITH IMPAIRED SYSTEMIC IMMUNITY AND EPIGENETIC MODIFICATIONS IN A KEY LOCUS INVOLVED IN ATOPY: FOXP3, WITH A HIGHER IMPACT ON ATOPIC CHILDREN. THE RESULTS SUGGEST THAT INCREASED ATOPIC CLINICAL SYMPTOMS IN CHILDREN COULD BE LINKED TO INCREASED PAH EXPOSURE IN AIR POLLUTION.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
4  1916  40 ENVIRONMENTAL AND OCCUPATIONAL EXPOSURE TO CHEMICALS AND TELOMERE LENGTH IN HUMAN STUDIES. TELOMERES ARE COMPLEXES OF TANDEM REPEATS OF DNA (5'-TTAGGG-3') AND PROTEIN THAT CAP EUKARYOTIC CHROMOSOMES AND PLAY A CRITICAL ROLE IN CHROMOSOME STABILITY. TELOMERES SHORTEN WITH AGING AND THIS PROCESS CAN BE ACCELERATED BY INCREASED OXIDATIVE STRESS AND EPISODES OF INFLAMMATION. EVIDENCE IS RAPIDLY GROWING THAT TELOMERE LENGTH (TL) MAY BE AFFECTED BY ENVIRONMENTAL CHEMICALS THAT HAVE FREQUENTLY BEEN ASSOCIATED WITH CHRONIC DISEASES. IN THIS ARTICLE, WE REVIEW THE PUBLISHED DATA ON TL IN RELATION TO ENVIRONMENTAL AND OCCUPATIONAL EXPOSURE TO SEVERAL CHEMICALS BASED ON OUR OWN AND OTHERS' STUDIES. THE ENVIRONMENTAL AND OCCUPATIONAL EXPOSURES ASSOCIATED WITH SHORTER TL INCLUDE TRAFFIC-RELATED AIR POLLUTION (IE, PARTICULATE MATTER (PM), BLACK CARBON (BC), AND BENZENE AND TOLUENE), POLYCYCLIC AROMATIC HYDROCARBONS (PAHS), N-NITROSAMINES, PESTICIDES, LEAD, EXPOSURE IN CAR MECHANICAL WORKSHOPS, AND HAZARDOUS WASTE EXPOSURE. ARSENIC, PERSISTENT ORGANIC POLLUTANTS (POPS) AND SHORT-TERM EXPOSURE TO PM ARE ASSOCIATED WITH LONGER TL. WE DISCUSS THE POSSIBLE REASONS FOR THE DIFFERENCES IN RESULTS, INCLUDING TIME- AND DOSE-RELATED ISSUES, STUDY DESIGN, AND POSSIBLE MECHANISMS INVOLVED IN TELOMERE REGULATION. WE ALSO DISCUSS THE FUTURE DIRECTIONS AND CHALLENGES FOR TL-RELATED ENVIRONMENTAL AND OCCUPATIONAL HEALTH RESEARCH, SUCH AS INVESTIGATION OF TL IN SUBPOPULATIONS OF BLOOD LEUKOCYTES, AND THE STUDY OF GENETIC AND EPIGENETIC FACTORS THAT MAY REGULATE TELOMERE INTEGRITY USING LONGITUDINAL DESIGNS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
5  6492  47 TRAFFIC-RELATED AIR POLLUTION AND GROUND-LEVEL OZONE ASSOCIATED GLOBAL DNA HYPOMETHYLATION AND BULKY DNA ADDUCT FORMATION. STUDIES HAVE INDICATED THAT AIR POLLUTION, INCLUDING SURFACE-LEVEL OZONE (O(3)), CAN SIGNIFICANTLY INFLUENCE THE RISK OF CHRONIC DISEASES. TO BETTER UNDERSTAND THE CARCINOGENIC MECHANISMS OF AIR POLLUTANTS AND IDENTIFY PREDICTIVE DISEASE BIOMARKERS, WE EXAMINED THE ASSOCIATION BETWEEN TRAFFIC-RELATED POLLUTANTS WITH DNA METHYLATION ALTERATIONS AND BULKY DNA ADDUCTS, TWO BIOMARKERS OF CARCINOGEN EXPOSURE AND CANCER RISK, IN THE PERIPHERAL BLOOD OF 140 VOLUNTEERS-95 TRAFFIC POLICE OFFICERS, AND 45 UNEXPOSED SUBJECTS. THE DNA METHYLATION AND ADDUCT MEASUREMENTS WERE PERFORMED BY BISULFITE-PCR AND PYROSEQUENCING AND (32)P-POSTLABELING ASSAY. AIRBORNE LEVELS OF BENZO(A)PYRENE [B(A)P], CARBON MONOXIDE, AND TROPOSPHERIC O(3) WERE DETERMINED BY PERSONAL EXPOSURE BIOMONITORING OR BY FIXED MONITORING STATIONS. OVERALL, AIR POLLUTION EXPOSURE WAS ASSOCIATED WITH A SIGNIFICANT REDUCTION (1.41 UNITS) IN GLOBAL DNA METHYLATION (95% C.I. -2.65-0.04, P = 0.026). THE DECREMENT IN ALU REPETITIVE ELEMENTS WAS GREATEST IN THE POLICEMEN WORKING DOWNTOWN (95% C.I. -3.23--0.49, P = 0.008). THE DNA ADDUCTS WERE FOUND TO BE SIGNIFICANTLY INCREASED (0.45 UNITS) IN THE MUNICIPAL OFFICERS WITH RESPECT TO UNEXPOSED SUBJECTS (95% C.I. 0.02-0.88, P = 0.039), MAINLY IN THOSE WHO WERE CONTROLLING TRAFFIC IN DOWNTOWN AREAS (95% C.I. 0.39-1.29, P < 0.001). REGRESSION MODELS INDICATED AN INCREMENT OF ALU METHYLATION AT HIGHER B(A)P CONCENTRATIONS (95% C.I. 0.03-0.60, P = 0.032). MOREOVER, STATISTICAL MODELS SHOWED A DECREMENT IN ALU METHYLATION AND AN INCREMENT OF DNA DAMAGE ONLY ABOVE THE CUT-OFF VALUE OF 30 MICROG/M(3) O(3). A SIGNIFICANT INCREMENT OF 0.73 UNITS OF IL-6 GENE METHYLATION WAS ALSO FOUND IN SMOKERS WITH RESPECT TO NON-SMOKERS. OUR RESULTS HIGHLIGHTED THE ROLE OF AIR POLLUTION ON EPIGENETIC ALTERATIONS AND GENOTOXIC EFFECTS, ESPECIALLY ABOVE THE TARGET VALUE OF 30 MICROG/M(3) SURFACE-LEVEL O(3), SUPPORTING THE NECESSITY FOR DEVELOPING PUBLIC HEALTH STRATEGIES AIMED TO REDUCE TRAFFIC-RELATED AIR POLLUTION MOLECULAR ALTERATIONS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
6  3710  45 INFLUENCES OF POLYCYCLIC AROMATIC HYDROCARBON ON THE EPIGENOME TOXICITY AND ITS APPLICABILITY IN HUMAN HEALTH RISK ASSESSMENT. THE EXISTENCE OF POLYCYCLIC AROMATIC HYDROCARBONS (PAHS) IN AMBIENT AIR IS AN ESCALATING CONCERN WORLDWIDE BECAUSE OF THEIR ABILITY TO CAUSE CANCER AND INDUCE PERMANENT CHANGES IN THE GENETIC MATERIAL. GROWING EVIDENCE IMPLIES THAT DURING EARLY LIFE-SENSITIVE STAGES, THE RISK OF PROGRESSION OF ACUTE AND CHRONIC DISEASES DEPENDS ON EPIGENETIC CHANGES INITIATED BY THE INFLUENCE OF ENVIRONMENTAL CUES. SEVERAL REPORTS DECIPHERED THE RELATIONSHIP BETWEEN EXPOSURE TO ENVIRONMENTAL CHEMICALS AND EPIGENETICS, AND HAVE KNOWN TOXICANTS THAT ALTER THE EPIGENETIC STATES. AMONGST PAHS, BENZO[A]PYRENE (B[A]P) IS ACCEPTED AS A GROUP 1 CANCER-CAUSING AGENT BY THE INTERNATIONAL AGENCY FOR THE RESEARCH ON CANCER (IARC). B[A]P IS A WELL-STUDIED PRO-CARCINOGEN THAT IS METABOLICALLY ACTIVATED BY THE ARYL HYDROCARBON RECEPTOR (AHR)/CYTOCHROME P450 PATHWAY. CYTOCHROME P450 PLAYS A PIVOTAL ROLE IN THE STIMULATION STEP, WHICH IS ESSENTIAL FOR DNA ADDUCT FORMATION. ACCRUING EVIDENCE SUGGESTS THAT EPIGENETIC ALTERATIONS ASSUME A FUNDAMENTAL PART IN PAH-PROMOTED CARCINOGENESIS. THIS INTERACTION BETWEEN PAHS AND EPIGENETIC FACTORS RESULTS IN AN ALTERED PROFILE OF THESE MARKS, GLOBALLY AND LOCUS-SPECIFIC. SOME OF THE EPIGENETIC CHANGES DUE TO EXPOSURE TO PAHS LEAD TO INCREASED DISEASE SUSCEPTIBILITY AND PROGRESSION. IT IS WELL UNDERSTOOD THAT EXPOSURE TO ENVIRONMENTAL CARCINOGENS, SUCH AS PAH TRIGGERS DISEASE PATHWAYS THROUGH CHANGES IN THE GENOME. SEVERAL EVIDENCE REPORTED DUE TO THE EPIGENOME-WIDE ASSOCIATION STUDIES, THAT EARLY LIFE ADVERSE ENVIRONMENTAL EVENTS MAY TRIGGER WIDESPREAD AND PERSISTENT VARIATIONS IN TRANSCRIPTIONAL PROFILING. MOREOVER, THESE VARIATIONS RESPOND TO DNA DAMAGE AND/OR A CONSEQUENCE OF EPIGENETIC MODIFICATIONS THAT NEED FURTHER INVESTIGATION. GROWING EVIDENCE HAS ASSOCIATED PAHS WITH EPIGENETIC VARIATIONS INVOLVING ALTERATIONS IN DNA METHYLATION, HISTONE MODIFICATION, AND MICRO RNA (MIRNA) REGULATION. EPIGENETIC ALTERATIONS TO PAH EXPOSURE WERE RELATED TO CHRONIC DISEASES, SUCH AS PULMONARY DISEASE, CARDIOVASCULAR DISEASE, ENDOCRINE DISRUPTOR, NERVOUS SYSTEM DISORDER, AND CANCER. THIS HORMETIC RESPONSE GIVES A NOVEL PERCEPTION CONCERNING THE TOXICITY OF PAHS AND THE BIOLOGICAL REACTION THAT MAY BE A DISTINCT RELIANCE ON EXPOSURE. THIS REVIEW SHEDS LIGHT ON UNDERSTANDING THE LATEST EVIDENCE ABOUT HOW PAHS CAN ALTER EPIGENETIC PATTERNS AND HUMAN HEALTH. IN CONCLUSION, AS SEVERAL EPIGENETIC CHANGE MECHANISMS REMAIN UNCLEAR YET, FURTHER ANALYSES DERIVED FROM PAHS EXPOSURE MUST BE PERFORMED TO FIND NEW TARGETS AND DISEASE BIOMARKERS. IN SPITE OF THE CURRENT LIMITATIONS, NUMEROUS EVIDENCE SUPPORTS THE PERCEPTION THAT EPIGENETICS GRIPS SUBSTANTIAL POTENTIAL FOR ADVANCING OUR KNOWLEDGE ABOUT THE MOLECULAR MECHANISMS OF ENVIRONMENTAL TOXICANTS, ALSO FOR PREDICTING HEALTH-ASSOCIATED RISKS DUE TO ENVIRONMENTAL CIRCUMSTANCES EXPOSURE AND INDIVIDUAL SUSCEPTIBILITY.	2022	

7  5187  32 PRENATAL AIRBORNE POLYCYCLIC AROMATIC HYDROCARBON EXPOSURE, ALTERED REGULATION OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA (PPAR)GAMMA, AND LINKS WITH MAMMARY CANCER. ENVIRONMENTAL EXPOSURE TO POLYCYCLIC AROMATIC HYDROCARBONS (PAH) HAS BEEN SHOWN TO BE ASSOCIATED WITH CHRONIC DISEASE OUTCOMES THROUGH MULTIPLE MECHANISMS INCLUDING ALTERED REGULATION OF THE TRANSCRIPTION FACTOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA (PPAR) GAMMA. BECAUSE PAH EXPOSURE AND PPARGAMMA EACH HAVE BEEN ASSOCIATED WITH MAMMARY CANCER, WE ASKED WHETHER PAH WOULD INDUCE ALTERED REGULATION OF PPARGAMMA IN MAMMARY TISSUE, AND WHETHER THIS ASSOCIATION MAY UNDERLIE THE ASSOCIATION BETWEEN PAH AND MAMMARY CANCER. PREGNANT MICE WERE EXPOSED TO AEROSOLIZED PAH AT PROPORTIONS THAT MIMIC EQUIVALENT HUMAN EXPOSURES IN NEW YORK CITY AIR. WE HYPOTHESIZED THAT PRENATAL PAH EXPOSURE WOULD ALTER PPARGAMMA DNA METHYLATION AND GENE EXPRESSION AND INDUCE THE EPITHELIAL TO MESENCHYMAL TRANSITION (EMT) IN MAMMARY TISSUE OF OFFSPRING (F1) AND GRANDOFFSPRING (F2) MICE. WE ALSO HYPOTHESIZED THAT ALTERED REGULATION OF PPARGAMMA IN MAMMARY TISSUE WOULD ASSOCIATE WITH BIOMARKERS OF EMT, AND EXAMINED ASSOCIATIONS WITH WHOLE BODY WEIGHT. WE FOUND THAT PRENATAL PAH EXPOSURE LOWERED PPARGAMMA MAMMARY TISSUE METHYLATION AMONG GRANDOFFSPRING MICE AT POSTNATAL DAY (PND) 28. HOWEVER, PAH EXPOSURE DID NOT ASSOCIATE WITH ALTERED PPARGAMMA GENE EXPRESSION OR CONSISTENTLY WITH BIOMARKERS OF EMT. FINALLY, LOWER PPARGAMMA METHYLATION, BUT NOT GENE EXPRESSION, WAS ASSOCIATED WITH HIGHER BODY WEIGHT AMONG OFFSPRING AND GRANDOFFSPRING MICE AT PND28 AND PND60. FINDINGS SUGGEST ADDITIONAL EVIDENCE OF MULTI-GENERATIONAL ADVERSE EPIGENETIC EFFECTS OF PRENATAL PAH EXPOSURE AMONG GRANDOFFSPRING MICE.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
8   299  33 AIR POLLUTION AND DNA METHYLATION: EFFECTS OF EXPOSURE IN HUMANS. AIR POLLUTION EXPOSURE IS ESTIMATED TO CONTRIBUTE TO APPROXIMATELY SEVEN MILLION EARLY DEATHS EVERY YEAR WORLDWIDE AND MORE THAN 3% OF DISABILITY-ADJUSTED LIFE YEARS LOST. AIR POLLUTION HAS NUMEROUS HARMFUL EFFECTS ON HEALTH AND CONTRIBUTES TO THE DEVELOPMENT AND MORBIDITY OF CARDIOVASCULAR DISEASE, METABOLIC DISORDERS, AND A NUMBER OF LUNG PATHOLOGIES, INCLUDING ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). EMERGING DATA INDICATE THAT AIR POLLUTION EXPOSURE MODULATES THE EPIGENETIC MARK, DNA METHYLATION (DNAM), AND THAT THESE CHANGES MIGHT IN TURN INFLUENCE INFLAMMATION, DISEASE DEVELOPMENT, AND EXACERBATION RISK. SEVERAL TRAFFIC-RELATED AIR POLLUTION (TRAP) COMPONENTS, INCLUDING PARTICULATE MATTER (PM), BLACK CARBON (BC), OZONE (O(3)), NITROGEN OXIDES (NO(X)), AND POLYAROMATIC HYDROCARBONS (PAHS), HAVE BEEN ASSOCIATED WITH CHANGES IN DNAM; TYPICALLY LOWERING DNAM AFTER EXPOSURE. EFFECTS OF AIR POLLUTION ON DNAM HAVE BEEN OBSERVED ACROSS THE HUMAN LIFESPAN, BUT IT IS NOT YET CLEAR WHETHER EARLY LIFE DEVELOPMENTAL SENSITIVITY OR THE ACCUMULATION OF EXPOSURES HAVE THE MOST SIGNIFICANT EFFECTS ON HEALTH. AIR POLLUTION EXPOSURE-ASSOCIATED DNAM PATTERNS ARE OFTEN CORRELATED WITH LONG-TERM NEGATIVE RESPIRATORY HEALTH OUTCOMES, INCLUDING THE DEVELOPMENT OF LUNG DISEASES, A FOCUS IN THIS REVIEW. RECENTLY, INTERVENTIONS SUCH AS EXERCISE AND B VITAMINS HAVE BEEN PROPOSED TO REDUCE THE IMPACT OF AIR POLLUTION ON DNAM AND HEALTH. ULTIMATELY, IMPROVED KNOWLEDGE OF HOW EXPOSURE-INDUCED CHANGE IN DNAM IMPACTS HEALTH, BOTH ACUTELY AND CHRONICALLY, MAY ENABLE PREVENTATIVE AND REMEDIAL STRATEGIES TO REDUCE MORBIDITY IN POLLUTED ENVIRONMENTS.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
9   298  30 AIR POLLUTION AND AIRWAY DISEASE. EPIDEMIOLOGICAL AND TOXICOLOGICAL RESEARCH CONTINUES TO SUPPORT A LINK BETWEEN URBAN AIR POLLUTION AND AN INCREASED INCIDENCE AND/OR SEVERITY OF AIRWAY DISEASE. DETRIMENTAL EFFECTS OF OZONE (O(3)), NITROGEN DIOXIDE (NO(2)) AND PARTICULATE MATTER (PM), AS WELL AS TRAFFIC-RELATED POLLUTION AS A WHOLE, ON RESPIRATORY SYMPTOMS AND FUNCTION ARE WELL DOCUMENTED. NOT ONLY DO WE HAVE STRONG EPIDEMIOLOGICAL EVIDENCE OF A RELATIONSHIP BETWEEN AIR POLLUTION AND EXACERBATION OF ASTHMA AND RESPIRATORY MORBIDITY AND MORTALITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), BUT RECENT STUDIES, PARTICULARLY IN URBAN AREAS, HAVE SUGGESTED A ROLE FOR POLLUTANTS IN THE DEVELOPMENT OF BOTH ASTHMA AND COPD. SIMILARLY, WHILE PREVALENCE AND SEVERITY OF ATOPIC CONDITIONS APPEAR TO BE MORE COMMON IN URBAN COMPARED WITH RURAL COMMUNITIES, EVIDENCE IS EMERGING THAT TRAFFIC-RELATED POLLUTANTS MAY CONTRIBUTE TO THE DEVELOPMENT OF ALLERGY. FURTHERMORE, NUMEROUS EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES SUGGEST AN ASSOCIATION BETWEEN EXPOSURE TO NO(2) , O(3) , PM AND COMBUSTION PRODUCTS OF BIOMASS FUELS AND AN INCREASED SUSCEPTIBILITY TO AND MORBIDITY FROM RESPIRATORY INFECTION. GIVEN THE CONSIDERABLE CONTRIBUTION THAT TRAFFIC EMISSIONS MAKE TO URBAN AIR POLLUTION RESEARCHERS HAVE SOUGHT TO CHARACTERIZE THE RELATIVE TOXICITY OF TRAFFIC-RELATED PM POLLUTANTS. RECENT ADVANCES IN MECHANISMS IMPLICATED IN THE ASSOCIATION OF AIR POLLUTANTS AND AIRWAY DISEASE INCLUDE EPIGENETIC ALTERATION OF GENES BY COMBUSTION-RELATED POLLUTANTS AND HOW POLYMORPHISMS IN GENES INVOLVED IN ANTIOXIDANT PATHWAYS AND AIRWAY INFLAMMATION CAN MODIFY RESPONSES TO AIR POLLUTION EXPOSURES. OTHER INTERESTING EPIDEMIOLOGICAL OBSERVATIONS RELATED TO INCREASED HOST SUSCEPTIBILITY INCLUDE A POSSIBLE LINK BETWEEN CHRONIC PM EXPOSURE DURING CHILDHOOD AND VULNERABILITY TO COPD IN ADULTHOOD, AND THAT INFANTS SUBJECTED TO HIGHER PRENATAL LEVELS OF AIR POLLUTION MAY BE AT GREATER RISK OF DEVELOPING RESPIRATORY CONDITIONS. WHILE THE CHARACTERIZATION OF POLLUTANT COMPONENTS AND SOURCES PROMISE TO GUIDE POLLUTION CONTROL STRATEGIES, THE IDENTIFICATION OF SUSCEPTIBLE SUBPOPULATIONS WILL BE NECESSARY IF TARGETED THERAPY/PREVENTION OF POLLUTION-INDUCED RESPIRATORY DISEASES IS TO BE DEVELOPED.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
10  1223  36 CRITICAL REVIEW ON EMERGING HEALTH EFFECTS ASSOCIATED WITH THE INDOOR AIR QUALITY AND ITS SUSTAINABLE MANAGEMENT. INDOOR AIR QUALITY (IAQ) IS ONE OF THE FUNDAMENTAL ELEMENTS AFFECTING PEOPLE'S HEALTH AND WELL-BEING. CURRENTLY, THERE IS A LACK OF AWARENESS AMONG PEOPLE ABOUT THE QUANTIFICATION, IDENTIFICATION, AND POSSIBLE HEALTH EFFECTS OF IAQ. AIRBORNE POLLUTANTS SUCH AS VOLATILE ORGANIC COMPOUNDS (VOCS), PARTICULATE MATTER (PM), SULFUR DIOXIDE (SO2), CARBON MONOXIDE (CO), NITROUS OXIDE (NO), POLYCYCLIC AROMATIC HYDROCARBONS (PAHS) MICROBIAL SPORES, POLLEN, ALLERGENS, ETC. PRIMARILY CONTRIBUTE TO IAQ DETERIORATION. THIS REVIEW DISCUSSES THE SOURCES OF MAJOR INDOOR AIR POLLUTANTS, MOLECULAR TOXICITY MECHANISMS, AND THEIR EFFECTS ON CARDIOVASCULAR, OCULAR, NEUROLOGICAL, WOMEN, AND FOETAL HEALTH. ADDITIONALLY, CONTEMPORARY STRATEGIES AND SUSTAINABLE METHODS FOR REGULATING AND REDUCING POLLUTANT CONCENTRATIONS ARE EMPHASIZED, AND CURRENT INITIATIVES TO ADDRESS AND ENHANCE IAQ ARE EXPLORED, ALONG WITH THEIR UNIQUE ADVANTAGES AND POTENTIALS. DUE TO THEIR LONGER EXPOSURE TIMES AND PARTICULAR PHYSICAL CHARACTERISTICS, WOMEN AND CHILDREN ARE MORE AT RISK FOR POOR INDOOR AIR QUALITY. BY TRIGGERING MANY TOXICITY MECHANISMS, INCLUDING OXIDATIVE STRESS, DNA METHYLATION, EPIGENETIC MODIFICATIONS, AND GENE ACTIVATION, INDOOR AIR POLLUTION CAN CAUSE A RANGE OF HEALTH ISSUES. LOW BIRTH WEIGHT, ACUTE LOWER RESPIRATORY TRACT INFECTIONS, SICK BUILDING SYNDROMES (SBS), AND EARLY DEATH ARE MORE PREVALENT IN EXPOSED RESIDENTS. ON THE OTHER HAND, THE MAIN CAUSES OF INCAPACITY AND EARLY MORTALITY ARE LUNG CANCER, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, AND CARDIOVASCULAR DISORDERS. IT'S CRUCIAL TO ACKNOWLEDGE ANTICIPATED RESEARCH NEEDS AND IMPLEMENTED EFFICIENT INTERVENTIONS AND POLICIES TO LOWER HEALTH HAZARDS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
11  3063  30 GENOME-WIDE DNA METHYLATION AND LONG-TERM AMBIENT AIR POLLUTION EXPOSURE IN KOREAN ADULTS. BACKGROUND: AMBIENT AIR POLLUTION IS ASSOCIATED WITH NUMEROUS ADVERSE HEALTH OUTCOMES, BUT THE UNDERLYING MECHANISMS ARE NOT WELL UNDERSTOOD; EPIGENETIC EFFECTS INCLUDING ALTERED DNA METHYLATION COULD PLAY A ROLE. TO EVALUATE ASSOCIATIONS OF LONG-TERM AIR POLLUTION EXPOSURE WITH DNA METHYLATION IN BLOOD, WE CONDUCTED AN EPIGENOME-WIDE ASSOCIATION STUDY IN A KOREAN CHRONIC OBSTRUCTIVE PULMONARY DISEASE COHORT (N = 100 INCLUDING 60 CASES) USING ILLUMINA'S INFINIUM HUMANMETHYLATION450K BEADCHIP. ANNUAL AVERAGE CONCENTRATIONS OF PARTICULATE MATTER </= 10 MUM IN DIAMETER (PM(10)) AND NITROGEN DIOXIDE (NO(2)) WERE ESTIMATED AT PARTICIPANTS' RESIDENTIAL ADDRESSES USING EXPOSURE PREDICTION MODELS. WE USED ROBUST LINEAR REGRESSION TO IDENTIFY DIFFERENTIALLY METHYLATED PROBES (DMPS) AND TWO DIFFERENT APPROACHES, DMRCATE AND COMB-P, TO IDENTIFY DIFFERENTIALLY METHYLATED REGIONS (DMRS). RESULTS: AFTER MULTIPLE TESTING CORRECTION (FALSE DISCOVERY RATE < 0.05), THERE WERE 12 DMPS AND 27 DMRS ASSOCIATED WITH PM(10) AND 45 DMPS AND 57 DMRS RELATED TO NO(2). DMP CG06992688 (OTUB2) AND SEVERAL DMRS WERE ASSOCIATED WITH BOTH EXPOSURES. ELEVEN DMPS IN RELATION TO NO(2) CONFIRMED PREVIOUS FINDINGS IN EUROPEANS; THE REMAINDER WERE NOVEL. METHYLATION LEVELS OF 39 DMPS WERE ASSOCIATED WITH EXPRESSION LEVELS OF NEARBY GENES IN A SEPARATE DATASET OF 3075 INDIVIDUALS. ENRICHED NETWORKS WERE RELATED TO OUTCOMES ASSOCIATED WITH AIR POLLUTION INCLUDING CARDIOVASCULAR AND RESPIRATORY DISEASES AS WELL AS INFLAMMATORY AND IMMUNE RESPONSES. CONCLUSIONS: THIS STUDY PROVIDES EVIDENCE THAT LONG-TERM AMBIENT AIR POLLUTION EXPOSURE IMPACTS DNA METHYLATION. THE DIFFERENTIAL METHYLATION SIGNALS CAN SERVE AS POTENTIAL AIR POLLUTION BIOMARKERS. THESE RESULTS MAY HELP BETTER UNDERSTAND THE INFLUENCES OF AMBIENT AIR POLLUTION ON HUMAN HEALTH.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
12   906  28 CHRONIC EXPOSURE TO ENVIRONMENTAL LEVEL PHENANTHRENE INDUCES NON-OBESITY-DEPENDENT INSULIN RESISTANCE IN MALE MICE. EPIDEMIOLOGICAL EVIDENCE SHOWS THAT THE BODY BURDEN OF POLYCYCLIC AROMATIC HYDROCARBONS (PAHS) IS RELATED TO THE DISRUPTION OF GLUCOSE HOMEOSTASIS. HOWEVER, THE CONTRIBUTION OF PAHS TO THE DEVELOPMENT OF DIABETES REMAINS POORLY DOCUMENTED. IN THE CURRENT WORK, MALE KUNMING MICE RECEIVED PHENANTHRENE (PHE) (5, 50, AND 500 NG/KG) BY GAVAGE ADMINISTRATION ONCE EVERY 2 DAYS FOR 28 WEEKS. THE SIGNIFICANT ELEVATION OF HOMEOSTASIS MODEL ASSESSMENT-INSULIN RESISTANCE (HOMA-IR) AND HOMA-BETA CELL, ACCOMPANIED BY HYPERINSULINEMIA, INDICATED THE OCCURRENCE OF INSULIN RESISTANCE. THE SUPPRESSION OF THE INSULIN RECEPTOR SIGNALING PATHWAY IN SKELETAL MUSCLE MIGHT BE RESPONSIBLE FOR GLUCOSE INTOLERANCE. UNDER THE NONOBESE STATE, THE SERUM LEVELS OF RESISTIN, TUMOR NECROSIS FACTOR-ALPHA, AND INTERLEUKIN-6 WERE ELEVATED, WHEREAS THE LEVELS OF ADIPONECTIN WERE REDUCED. THESE CHANGES IN ADIPOCYTOKINE LEVELS WERE CONSISTENT WITH THEIR TRANSCRIPTION IN WHITE ADIPOSE TISSUE. THE PROMOTER METHYLATION LEVELS OF RETN (ENCODING RESISTIN) AND ADIPOQ (ENCODING ADIPONECTIN) WERE INVERSELY CORRELATED WITH THEIR MRNA LEVELS, INDICATING THAT PHE EXPOSURE COULD CAUSE THE DISRUPTION OF ADIPOCYTOKINE SECRETION VIA EPIGENETIC MODIFICATION. THE RESULTS WOULD BE HELPFUL FOR UNDERSTANDING THE PATHOGENESIS IN THE DEVELOPMENT OF T2DM CAUSED BY NONOBESOGENIC POLLUTANTS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
13   363  26 AMBIENT AIR POLLUTION: HEALTH HAZARDS TO CHILDREN. AMBIENT AIR POLLUTION IS PRODUCED BY SOURCES INCLUDING VEHICULAR TRAFFIC, COAL-FIRED POWER PLANTS, HYDRAULIC FRACTURING, AGRICULTURAL PRODUCTION, AND FOREST FIRES. IT CONSISTS OF PRIMARY POLLUTANTS GENERATED BY COMBUSTION AND SECONDARY POLLUTANTS FORMED IN THE ATMOSPHERE FROM PRECURSOR GASES. AIR POLLUTION CAUSES AND EXACERBATES CLIMATE CHANGE, AND CLIMATE CHANGE WORSENS HEALTH EFFECTS OF AIR POLLUTION. INFANTS AND CHILDREN ARE UNIQUELY SENSITIVE TO AIR POLLUTION, BECAUSE THEIR ORGANS ARE DEVELOPING AND THEY HAVE HIGHER AIR PER BODY WEIGHT INTAKE. HEALTH EFFECTS LINKED TO AIR POLLUTION INCLUDE NOT ONLY EXACERBATIONS OF RESPIRATORY DISEASES BUT ALSO REDUCED LUNG FUNCTION DEVELOPMENT AND INCREASED ASTHMA INCIDENCE. ADDITIONAL OUTCOMES OF CONCERN INCLUDE PRETERM BIRTH, LOW BIRTH WEIGHT, NEURODEVELOPMENTAL DISORDERS, IQ LOSS, PEDIATRIC CANCERS, AND INCREASED RISKS FOR ADULT CHRONIC DISEASES. THESE EFFECTS ARE MEDIATED BY OXIDATIVE STRESS, CHRONIC INFLAMMATION, ENDOCRINE DISRUPTION, AND GENETIC AND EPIGENETIC MECHANISMS ACROSS THE LIFE SPAN. NATURAL EXPERIMENTS DEMONSTRATE THAT WITH INITIATIVES SUCH AS INCREASED USE OF PUBLIC TRANSPORTATION, BOTH AIR QUALITY AND COMMUNITY HEALTH IMPROVE. SIMILARLY, THE CLEAN AIR ACT HAS IMPROVED AIR QUALITY, ALTHOUGH EXPOSURE INEQUITIES PERSIST. OTHER EFFECTIVE STRATEGIES FOR REDUCING AIR POLLUTION INCLUDE ENDING RELIANCE ON COAL, OIL, AND GAS; REGULATING INDUSTRIAL EMISSIONS; REDUCING EXPOSURE WITH ATTENTION TO PROXIMITY OF RESIDENCES, SCHOOLS, AND CHILD CARE FACILITIES TO TRAFFIC; AND A GREATER AWARENESS OF THE AIR QUALITY INDEX. THIS POLICY REVIEWS BOTH SHORT- AND LONG-TERM HEALTH CONSEQUENCES OF AMBIENT AIR POLLUTION, ESPECIALLY IN RELATION TO DEVELOPMENTAL EXPOSURES. IT EXAMINES INDIVIDUAL, COMMUNITY, AND LEGISLATIVE STRATEGIES TO MITIGATE AIR POLLUTION.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
14   974  45 CHRONIC OCCUPATIONAL EXPOSURE ENDURED BY TOBACCO FARMERS FROM BRAZIL AND ASSOCIATION WITH DNA DAMAGE. TOBACCO FARMING IS AN IMPORTANT ECONOMIC INCOME IN BRAZIL, ALTHOUGH IT HAS BEEN CHALLENGED AS REGARD THE OCCUPATIONAL EXPOSURE TO BOTH PESTICIDES AND NICOTINE ENDURED BY FARMERS. CHRONIC OCCUPATIONAL EXPOSURE TO COMPLEX MIXTURES CAN LEAD TO HEALTH HAZARDOUS. WE EXAMINED GENOMIC INSTABILITY AND EPIGENETIC CHANGES IN TOBACCO FARMERS OCCUPATIONALLY EXPOSED TO PESTICIDE MIXTURES AND NICOTINE AT TOBACCO FIELDS. DNA DAMAGE WAS ASSESSED BY ALKALINE COMET ASSAY IN BLOOD CELLS. GENOMIC DNA WAS ISOLATED, AND TELOMERE LENGTH WAS MEASURED USING QUANTITATIVE POLYMERASE CHAIN REACTION ASSAY. WE MEASURED 5-METHYL-2'-DEOXYCYTIDINE, A MARKER OF GLOBAL DNA METHYLATION, AND P16 PROMOTER METHYLATION. THE OXIDATIVE PROFILE WAS EVALUATED BY TROLOX EQUIVALENT ANTIOXIDANT CAPACITY AND LIPID PEROXIDATION (THIOBARBITURIC ACID REACTIVE SUBSTANCES) IN SERUM. EXPOSURE PARAMETERS, PLASMA COTININE AND INORGANIC ELEMENT LEVELS, WERE ALSO MEASURED. DNA DAMAGE WAS SIGNIFICANTLY ELEVATED FOR FARMERS IN RELATION TO UNEXPOSED GROUP (P < 0.001; MANN-WHITNEY TEST) AND POSITIVELY ASSOCIATED WITH YEARS OF EXPOSURE. INVERSE RELATIONSHIP BETWEEN DNA DAMAGE AND TOTAL EQUIVALENT ANTIOXIDANT ACTIVITY WAS DEMONSTRATED FOR EXPOSED AND UNEXPOSED GROUPS. EXPOSED GROUP SHOWED SIGNIFICANTLY SHORTER TELOMERES (P < 0.001; UNPAIRED T-TEST) AND DNA HYPOMETHYLATION (P < 0.001; UNPAIRED T-TEST), AS WELL AS P16 HYPERMETHYLATION (P = 0.003; MANN-WHITNEY TEST). LIPID PEROXIDATION WAS INCREASED FOR EXPOSED GROUP IN RELATION TO UNEXPOSED ONE (P = 0.02; MANN-WHITNEY TEST) AND PRESENTED A POSITIVE CORRELATION WITH GLOBAL DNA METHYLATION (P = 0.0264). FARMERS HAVE INCREASED PLASMA COTININE LEVELS (P < 0.001) AND INORGANIC ELEMENTS (PHOSPHORUS, SULPHUR AND CHLORINE) IN RELATION TO UNEXPOSED GROUP. ELEVATED OXIDATIVE STRESS LEVELS DUE TO CHRONIC OCCUPATIONAL PESTICIDE MIXTURES AND NICOTINE EXPOSURE IN TOBACCO FARMERS WERE ASSOCIATED WITH HIGHER DNA DAMAGE, SHORTER TELOMERES AND ALTERED DNA METHYLATION. TELOMERE-ACCELERATED ATTRITION DUE TO EXPOSURE MAY BE POTENTIAL INTERMEDIATE STEP BEFORE A DISEASE STATE.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
15  5960  42 TELOMERE LENGTH IN HEPATOCELLULAR CARCINOMA AND PAIRED ADJACENT NON-TUMOR TISSUES BY QUANTITATIVE PCR. TELOMERE SHORTENING LIMITS THE PROLIFERATIVE CAPACITY OF HUMAN CELLS, RESTRAINS THE REGENERATIVE CAPACITY OF ORGAN SYSTEMS DURING CHRONIC DISEASES AND AGING AND ALSO INDUCES CHROMOSOMAL INSTABILITY AS WELL AS INITIATION OF CANCER. PREVIOUS STUDIES DEMONSTRATED THAT TELOMERES ARE OFTEN SIGNIFICANTLY SHORTER IN TUMOR TISSUE, INCLUDING HEPATOCELLULAR CARCINOMA (HCC), COMPARED TO THE SURROUNDING TISSUE, BUT TELOMERE LENGTH IN HCC TISSUES WAS NOT CORRELATED WITH SEVERAL CLINICAL PARAMETERS, SUCH AS AGE, SEX, HBV OR HCV INFECTIONS AND TUMOR SIZE. IN THE PRESENT STUDY, THE TELOMERE LENGTH RATIO OF 36 PAIRED HCC, AND THEIR ADJACENT NON-TUMOR TISSUES WAS MEASURED BY QUANTITATIVE PCR (Q-PCR). THE MEAN TELOMERE LENGTHS (SD) FOR HCC AND ADJACENT NON-TUMOR TISSUES WERE 0.26 (0.10) AND 0.47 (0.20) RESPECTIVELY (T = 6.22, P < 0.0001). THERE WAS A LARGE DIFFERENCE IN THE DISTRIBUTION OF SUBJECTS BASED ON TELOMERE LENGTH IN TUMOR AND ADJACENT NON-TUMOR TISSUES. THE NUMBER OF TUMORS WITH TELOMERE LENGTH SHORTER THAN 0.50 WAS MUCH HIGHER THAN THAT OF ADJACENT NON-TUMOR TISSUES; MORE THAN 90% OF THE TISSUES WITH TELOMERE LENGTH > OR = 0.50 WERE ADJACENT NON-TUMOR TISSUES. THE CORRELATIONS BETWEEN TELOMERE LENGTH AND AFLATOXIN B1- AND POLYCYCLIC AROMATIC HYDROCARBON-DNA ADDUCTS LEVEL, P53 MUTATIONS AND P16 HYPERMETHYLATION STATUS WERE ALSO TESTED, BUT NO SIGNIFICANT ASSOCIATIONS WERE FOUND. THE RELATIONSHIP BETWEEN TELOMERE LENGTH SHORTENING, CHEMICAL CARCINOGEN EXPOSURE, AND GENETIC AND EPIGENETIC CHANGES IN HEPATOCARCINOGENESIS NEEDS FURTHER INVESTIGATION.	2007	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
16   642  35 BIOMARKERS OF PARTICULATE MATTER EXPOSURE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A SYSTEMATIC REVIEW. BACKGROUND: IN RECENT YEARS, AMBIENT PARTICULATE MATTER (PM) EXPOSURE HAS BEEN STRONGLY LINKED WITH HEALTH EFFECTS. ELEVATED LEVELS OF PM IN POLLUTED AIR HAVE BEEN CORRELATED WITH THE ONSET AND DEVELOPMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). THIS SYSTEMATIC REVIEW WAS CONDUCTED TO EVALUATE BIOMARKERS THAT COULD REFLECT THE EFFECTS OF PM EXPOSURE IN PATIENTS WITH COPD. METHODS: WE PERFORMED A SYSTEMATIC REVIEW OF STUDIES PUBLISHED ON BIOMARKERS ASSOCIATED WITH PM EXPOSURE IN PATIENTS WITH COPD BETWEEN JANUARY 01, 2012 AND JUNE 30, 2022 IN PUBMED/MEDLINE, EMBASE, AND COCHRANE DATABASES. STUDIES THAT INCLUDED DATA ON BIOMARKERS WITH COPD EXPOSED PM WERE ELIGIBLE FOR INCLUSION. BIOMARKERS WERE CLASSIFIED INTO 4 GROUPS ACCORDING TO THEIR MECHANISMS. RESULTS: OF THE 105 STUDIES IDENTIFIED, 22 WERE INCLUDED IN THIS STUDY. NEARLY 50 BIOMARKERS HAVE BEEN PROPOSED IN THE STUDIES INCLUDED IN THIS REVIEW, AND THE MOST STUDIED IN RELATION TO PM ARE SEVERAL INTERLEUKINS. VARIOUS MECHANISMS HAVE BEEN REPORTED BY WHICH PM INDUCES AND AGGRAVATES COPD. SIX STUDIES RELATED TO OXIDATIVE STRESS, ONE RELATED TO DIRECT EFFECT OF INNATE AND ADAPTIVE IMMUNE SYSTEMS, 16 ASSOCIATED WITH GENETIC REGULATION OF INFLAMMATION, AND TWO RELATED TO EPIGENETIC REGULATION OF PHYSIOLOGY AND SUSCEPTIBILITY WERE FOUND. BIOMARKERS RELATED TO THESE MECHANISMS WERE DETECTED IN SERUM, SPUTUM, URINE, EXHALED BREATH CONCENTRATION (EBC), AND SHOWED VARIOUS CORRELATIONS WITH PM IN COPD. CONCLUSIONS: VARIOUS BIOMARKERS HAVE SHOWN POTENTIAL IN PREDICTING THE EXTENT OF PM EXPOSURE IN COPD PATIENTS. FUTURE STUDIES ARE NEEDED TO ESTABLISH RECOMMENDATIONS FOR REGULATION TO REDUCE AIRBORNE PM, WHICH COULD BE USED TO DEVELOP STRATEGIES FOR PREVENTION AND MANAGEMENT OF ENVIRONMENTAL RESPIRATORY DISEASES.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
17  1140  27 CONCENTRATION OF FOLIC ACID (FA) IN SERUM OF JAPANESE PREGNANT WOMEN. OBJECTIVES EXPOSURE TO INORGANIC ARSENIC (IAS) IS A WORLD-WIDE HEALTH CONCERN. WE REPORTED THAT JAPANESE CHILDREN AND PREGNANT WOMEN ARE EXPOSED TO MODERATE LEVELS OF IAS THROUGH FOOD. REDUCING IAS CONTAMINATION FROM FOODS OF HIGH IAS IS AN IMPORTANT ISSUE UNIQUE IN JAPAN. INTEGRATED IAS IS METHYLATED TO LESS TOXIC ORGANIC FORMS, AND S-ADENOSYL-L-METHYONINE (SAM), A COMMON METHYL-DONOR OF DNA AND HISTONES, IS UTILIZED IN THIS PROCESS. CHRONIC CONSUMPTION OF SAM BY IAS METABOLISM DUE TO EXPOSURE TO IAS MIGHT ALTER THE EPIGENETIC MODIFICATION OF GENOME. THE SAM BIOSYNTHESIS PATHWAY IS DEPENDENT ON FOLATE CYCLE, AND IT IS POSSIBLE THAT INGESTION OF SUFFICIENT FOLIC ACID (FA) IS PROTECTIVE TO IAS INDUCED TOXICITY. METHODS IN THE COURSE OF OUR CROSS-SECTIONAL BODY BURDEN ANALYSES OF PB AND IAS IN JAPANESE CHILDREN AND PREGNANT WOMEN, TERMED "PBAS STUDY", FA CONCENTRATION IN SERUM OF 104 PREGNANT WOMEN WAS MEASURED. RESULTS MEAN (+/-SEM) OF SERUM FA CONCENTRATION WAS 15.8 +/- 1.3 (NG/ML). THERE ARE SIGNIFICANT NUMBER OF PEOPLE SHOWING VERY HIGH FA (>30 NG/ ML), AND LARGE FRACTION OF THEM WERE TAKING SUPPLEMENTS DAILY. CONCLUSIONS THESE RESULTS SUGGESTED THAT LEVEL OF FA INGESTION OF JAPANESE PREGNANT WOMEN IS HIGH FOR SUPPORTING NORMAL FETAL DEVELOPMENT.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
18  5957  31 TELOMERE LENGTH AND EPIGENETIC AGE ACCELERATION IN ADOLESCENTS WITH ANXIETY DISORDERS. EVIDENCE ON THE RELATIONSHIP BETWEEN GENETICS AND MENTAL HEALTH ARE FLOURISHING. HOWEVER, FEW STUDIES ARE EVALUATING EARLY BIOMARKERS THAT MIGHT LINK GENES, ENVIRONMENT, AND PSYCHOPATHOLOGY. WE AIMED TO STUDY TELOMERE LENGTH (TL) AND EPIGENETIC AGE ACCELERATION (AA) IN A COHORT OF ADOLESCENTS WITH AND WITHOUT ANXIETY DISORDERS (N = 234). WE EVALUATED A REPRESENTATIVE SUBSAMPLE OF PARTICIPANTS AT BASELINE AND AFTER 5 YEARS (N = 76) AND CATEGORIZED THEM ACCORDING TO THEIR ANXIETY DISORDER DIAGNOSIS AT BOTH TIME POINTS: (1) CONTROL GROUP (NO ANXIETY DISORDER, N = 18), (2) VARIABLE GROUP (ANXIETY DISORDER IN ONE EVALUATION, N = 38), AND (3) PERSISTENT GROUP (ANXIETY DISORDER AT BOTH TIME POINTS, N = 20). WE ASSESSED RELATIVE MEAN TL BY REAL-TIME QUANTITATIVE PCR AND DNA METHYLATION BY INFINIUM HUMANMETHYLATION450 BEADCHIP. WE CALCULATED AA USING THE HORVATH AGE ESTIMATION ALGORITHM AND ANALYZED DIFFERENCES AMONG GROUPS USING GENERALIZED LINEAR MIXED MODELS. THE PERSISTENT GROUP OF ANXIETY DISORDER DID NOT CHANGE TL OVER TIME (P = 0.495). THE VARIABLE GROUP HAD HIGHER BASELINE TL (P = 0.003) BUT NO ACCELERATED TL EROSION IN COMPARISON TO THE NON-ANXIETY CONTROL GROUP (P = 0.053). FURTHERMORE, THERE WERE NO DIFFERENCES IN AA AMONG GROUPS OVER TIME. OUR FINDINGS SUGGEST THAT ADOLESCENTS WITH CHRONIC ANXIETY DID NOT CHANGE TELOMERE LENGTH OVER TIME, WHICH COULD BE RELATED TO A DELAY IN NEURONAL DEVELOPMENT IN THIS PERIOD OF LIFE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
19   502  45 ASSOCIATION OF ARSENIC EXPOSURE WITH WHOLE BLOOD DNA METHYLATION: AN EPIGENOME-WIDE STUDY OF BANGLADESHI ADULTS. BACKGROUND: ARSENIC EXPOSURE AFFECTS [FORMULA: SEE TEXT] PEOPLE WORLDWIDE, INCLUDING [FORMULA: SEE TEXT] IN BANGLADESH. ARSENIC EXPOSURE INCREASES THE RISK OF CANCER AND OTHER CHRONIC DISEASES, AND ONE POTENTIAL MECHANISM OF ARSENIC TOXICITY IS EPIGENETIC DYSREGULATION. OBJECTIVE: WE ASSESSED ASSOCIATIONS BETWEEN ARSENIC EXPOSURE AND GENOME-WIDE DNA METHYLATION MEASURED AT BASELINE AMONG 396 BANGLADESHI ADULTS PARTICIPATING IN THE HEALTH EFFECTS OF ARSENIC LONGITUDINAL STUDY (HEALS) WHO WERE EXPOSED BY DRINKING NATURALLY CONTAMINATED WELL WATER. METHODS: METHYLATION IN WHOLE BLOOD DNA WAS MEASURED AT [FORMULA: SEE TEXT] USING THE ILLUMINA INFINIUMMETHYLATIONEPIC (EPIC) ARRAY. TO ASSESS ASSOCIATIONS BETWEEN ARSENIC EXPOSURE AND CPG METHYLATION, WE USED LINEAR REGRESSION MODELS ADJUSTED FOR COVARIATES AND SURROGATE VARIABLES (SVS) (CAPTURING UNKNOWN TECHNICAL AND BIOLOGIC FACTORS). WE ATTEMPTED REPLICATION AND CONDUCTED A META-ANALYSIS USING AN INDEPENDENT DATASET OF [FORMULA: SEE TEXT] FROM 400 BANGLADESHI INDIVIDUALS WITH ARSENICAL SKIN LESIONS. RESULTS: WE IDENTIFIED 34 CPGS ASSOCIATED WITH [FORMULA: SEE TEXT] CREATININE-ADJUSTED URINARY ARSENIC [[FORMULA: SEE TEXT]]. SIXTEEN OF THESE CPGS ANNOTATED TO THE [FORMULA: SEE TEXT] ARRAY, AND 10 ASSOCIATIONS WERE REPLICATED ([FORMULA: SEE TEXT]). THE TOP TWO CPGS ANNOTATED UPSTREAM OF THE ABR GENE (CG01912040, CG10003262 ). ALL URINARY ARSENIC-ASSOCIATED CPGS WERE ALSO ASSOCIATED WITH ARSENIC CONCENTRATION MEASURED IN DRINKING WATER ([FORMULA: SEE TEXT]). META-ANALYSIS ([FORMULA: SEE TEXT] SAMPLES) IDENTIFIED 221 URINARY ARSENIC-ASSOCIATED CPGS ([FORMULA: SEE TEXT]). THE ARSENIC-ASSOCIATED CPGS FROM THE META-ANALYSIS WERE ENRICHED IN NON-CPG ISLANDS AND SHORES ([FORMULA: SEE TEXT]) AND DEPLETED IN PROMOTER REGIONS ([FORMULA: SEE TEXT]). AMONG THE ARSENIC-ASSOCIATED CPGS ([FORMULA: SEE TEXT]), WE OBSERVED SIGNIFICANT ENRICHMENT OF GENES ANNOTATING TO THE REACTIVE OXYGEN SPECIES PATHWAY, INFLAMMATORY RESPONSE, AND TUMOR NECROSIS FACTOR [FORMULA: SEE TEXT] ([FORMULA: SEE TEXT]) SIGNALING VIA NUCLEAR FACTOR KAPPA-B ([FORMULA: SEE TEXT]) HALLMARKS ([FORMULA: SEE TEXT]). CONCLUSIONS: THE NOVEL AND REPLICABLE ASSOCIATIONS BETWEEN ARSENIC EXPOSURE AND DNA METHYLATION AT SPECIFIC CPGS OBSERVED IN THIS WORK SUGGEST THAT EPIGENETIC ALTERATIONS SHOULD BE FURTHER INVESTIGATED AS POTENTIAL MEDIATORS IN ARSENIC TOXICITY AND AS BIOMARKERS OF EXPOSURE AND EFFECT IN EXPOSED POPULATIONS. HTTPS://DOI.ORG/10.1289/EHP3849.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                         
20   361  27 AMBIENT AIR POLLUTION AND THROMBOSIS. AIR POLLUTION IS A GROWING PUBLIC HEALTH CONCERN OF GLOBAL SIGNIFICANCE. ACUTE AND CHRONIC EXPOSURE IS KNOWN TO IMPAIR CARDIOVASCULAR FUNCTION, EXACERBATE DISEASE AND INCREASE CARDIOVASCULAR MORTALITY. SEVERAL PLAUSIBLE BIOLOGICAL MECHANISMS HAVE BEEN PROPOSED FOR THESE ASSOCIATIONS, HOWEVER, AT PRESENT, THE PATHWAYS ARE INCOMPLETE. A SEMINAL REVIEW BY THE AMERICAN HEART ASSOCIATION (2010) CONCLUDED THAT THE THROMBOTIC EFFECTS OF PARTICULATE AIR POLLUTION LIKELY CONTRIBUTED TO THEIR EFFECTS ON CARDIOVASCULAR MORTALITY AND MORBIDITY. THE AIM OF THE CURRENT REVIEW IS TO APPRAISE THE NEWLY ACCUMULATED SCIENTIFIC EVIDENCE (2009-2016) ON CONTRIBUTION OF HAEMOSTASIS AND THROMBOSIS TOWARDS CARDIOVASCULAR DISEASE INDUCED BY EXPOSURE TO BOTH PARTICULATE AND GASEOUS POLLUTANTS.SEVENTY FOUR PUBLICATIONS WERE REVIEWED IN-DEPTH. THE WEIGHT OF EVIDENCE SUGGESTS THAT ACUTE EXPOSURE TO FINE PARTICULATE MATTER (PM(2.5)) INDUCES A SHIFT IN THE HAEMOSTATIC BALANCE TOWARDS A PRO-THROMBOTIC/PRO-COAGULATIVE STATE. INSUFFICIENT DATA WAS AVAILABLE TO ASCERTAIN IF A SIMILAR RELATIONSHIP EXISTS FOR GASEOUS POLLUTANTS, AND VERY FEW STUDIES HAVE ADDRESSED LONG-TERM EXPOSURE TO AMBIENT AIR POLLUTION. PLATELET ACTIVATION, OXIDATIVE STRESS, INTERPLAY BETWEEN INTERLEUKIN-6 AND TISSUE FACTOR, ALL APPEAR TO BE POTENTIALLY IMPORTANT MECHANISMS IN POLLUTION-MEDIATED THROMBOSIS, TOGETHER WITH AN EMERGING ROLE FOR CIRCULATING MICROVESICLES AND EPIGENETIC CHANGES.OVERALL, THE RECENT LITERATURE SUPPORTS, AND ARGUABLY STRENGTHENS, THE CONTENTION THAT AIR POLLUTION CONTRIBUTES TO CARDIOVASCULAR MORBIDITY BY PROMOTING HAEMOSTASIS. THE VOLUME AND DIVERSITY OF THE EVIDENCE HIGHLIGHTS THE COMPLEXITY OF THE PATHOPHYSIOLOGIC MECHANISMS BY WHICH AIR POLLUTION PROMOTES THROMBOSIS; MULTIPLE PATHWAYS ARE PLAUSIBLE AND IT IS MOST LIKELY THEY ACT IN CONCERT. FUTURE RESEARCH SHOULD ADDRESS THE ROLE GASEOUS POLLUTANTS PLAY IN THE CARDIOVASCULAR EFFECTS OF AIR POLLUTION MIXTURE AND DIRECT COMPARISON OF POTENTIALLY SUSCEPTIBLE GROUPS TO HEALTHY INDIVIDUALS.	2018