1 985 63 CHRONIC RADIATION EXPOSURE AS AN ECOLOGICAL FACTOR: HYPERMETHYLATION AND GENETIC DIFFERENTIATION IN IRRADIATED SCOTS PINE POPULATIONS. GENETIC AND EPIGENETIC CHANGES WERE INVESTIGATED IN CHRONICALLY IRRADIATED SCOTS PINE (PINUS SYLVESTRIS L.) POPULATIONS FROM TERRITORIES THAT WERE HEAVILY CONTAMINATED BY RADIONUCLIDES AS RESULT OF THE CHERNOBYL NUCLEAR POWER PLANT ACCIDENT. IN COMPARISON TO THE REFERENCE SITE, THE GENETIC DIVERSITY REVEALED BY ELECTROPHORETIC MOBILITY OF AFLPS WAS FOUND TO BE SIGNIFICANTLY HIGHER AT THE RADIOACTIVELY CONTAMINATED AREAS. IN ADDITION, THE GENOME OF PINE TREES WAS SIGNIFICANTLY HYPERMETHYLATED AT 4 OF THE 7 AFFECTED SITES. 2018 2 1115 33 COMPARATIVE ANALYSIS OF EPIGENETIC VARIABILITY IN TWO PINE SPECIES EXPOSED TO CHRONIC RADIATION IN THE CHERNOBYL AND FUKUSHIMA AFFECTED ZONES. COMPARATIVE ANALYSIS OF EPIGENETIC VARIABILITY IN TWO PINE SPECIES AFFECTED AS A RESULT OF THE CHERNOBYL AND FUKUSHIMA ACCIDENTS IS PRESENTED. THE ABSORBED DOSE RATE WITHIN THE AFFECTED CHERNOBYL SITES VARIES OVER A WIDER RANGE (1.5-24.6 MUGY/H) THAN WITHIN THE FUKUSHIMA SITES (3.5-6.5 MUGY/H). IT WAS SHOWN THAT CHRONIC IRRADIATION CAN CHANGE THE LEVEL OF WHOLE GENOME METHYLATION IN PINE POPULATIONS, BUT IN DIFFERENT WAYS. THE GENOMES OF JAPANESE RED PINES ARE HYPOMETHYLATED, AND THE DEGREE OF METHYLATION AND HYDROXYMETHYLATION DECREASES WITH AN INCREASE IN THE LEVEL OF RADIATION EXPOSURE. IN CONTRAST, THE PERCENTAGES OF GENOME METHYLATION AND HYDROXYMETHYLATION IN SCOTS PINE POPULATIONS EXCEED THE REFERENCE LEVELS. THE OBSERVED DISCREPANCY IN THE PATTERNS OF GENOME-WIDE DNA METHYLATION CAN BE ATTRIBUTED PARTLY TO THE DESIGN OF THE STUDY (DIFFERENCES IN THE CLIMATE, RADIATION DOSE, AGE AND SPECIES OF THE PINES) WHICH COULD AFFECT THE RESULTS. IN THE FRAME OF IRAP ANALYSIS, A LARGER NUMBER OF DIFFERENT BANDS WAS OBSERVED IN THE CHERNOBYL POPULATIONS COMPARED TO THE JAPANESE POPULATIONS. BOTH THE JAPANESE AND CHERNOBYL POPULATIONS ARE CHARACTERIZED BY SIGNIFICANT GENETIC VARIABILITY. HOWEVER, THE MAIN PART OF THIS VARIABILITY IS OBSERVED WITHIN POPULATIONS. THE DENDROGRAMS, BASED ON PRESENCE/ABSENCE OF IRAP FRAGMENTS AND NEI'S GENETIC DISTANCES, REVEALED SUBDIVISIONS OF THE CHERNOBYL AND JAPANESE POPULATIONS ACCORDING TO THE LEVEL OF RADIOACTIVE CONTAMINATION. ANALYSIS OF THE RESULTS PRESENTED WILL IMPROVE OUR UNDERSTANDING OF THE MECHANISMS UNDERLYING THE RESPONSES OF PINE TREES TO CHRONIC RADIATION EXPOSURE. 2023 3 3040 27 GENOME HYPERMETHYLATION IN PINUS SILVESTRIS OF CHERNOBYL--A MECHANISM FOR RADIATION ADAPTATION? ADAPTATION IS A COMPLEX PROCESS BY WHICH POPULATIONS OF ORGANISMS RESPOND TO LONG-TERM ENVIRONMENTAL STRESSES BY PERMANENT GENETIC CHANGE. HERE WE PRESENT DATA FROM THE NATURAL "OPEN-FIELD" RADIATION ADAPTATION EXPERIMENT AFTER THE CHERNOBYL ACCIDENT AND PROVIDE THE FIRST EVIDENCE OF THE INVOLVEMENT OF EPIGENETIC CHANGES IN ADAPTATION OF A EUKARYOTE-SCOTS PINE (PINUS SILVESTRIS), TO CHRONIC RADIATION EXPOSURE. WE HAVE EVALUATED GLOBAL GENOME METHYLATION OF CONTROL AND RADIATION-EXPOSED PINE TREES USING A METHOD BASED ON CLEAVAGE BY A METHYLATION-SENSITIVE HPAII RESTRICTION ENDONUCLEASE THAT LEAVES A 5' GUANINE OVERHANG AND SUBSEQUENT SINGLE NUCLEOTIDE EXTENSION WITH LABELED [3H] DCTP. WE HAVE FOUND THAT GENOMIC DNA OF EXPOSED PINE TREES WAS CONSIDERABLY HYPERMETHYLATED. MOREOVER, HYPERMETHYLATION APPEARED TO BE DEPENDENT UPON THE RADIATION DOSE ABSORBED BY THE TREES. SUCH HYPERMETHYLATION MAY BE VIEWED AS A DEFENSE STRATEGY OF PLANTS THAT PREVENTS GENOME INSTABILITY AND RESHUFFLING OF THE HEREDITARY MATERIAL, ALLOWING SURVIVAL IN AN EXTREME ENVIRONMENT. FURTHER STUDIES ARE CLEARLY NEEDED TO ANALYZE IN DETAIL THE INVOLVEMENT OF DNA METHYLATION AND OTHER EPIGENETIC MECHANISMS IN THE COMPLEX PROCESS OF RADIATION STRESS AND ADAPTIVE RESPONSE. 2003 4 1835 29 EFFECTS OF NON-HUMAN SPECIES IRRADIATION AFTER THE CHERNOBYL NPP ACCIDENT. THE AREA AFFECTED BY THE CHERNOBYL NUCLEAR POWER PLANT ACCIDENT IN 1986 HAS BECOME A UNIQUE TEST SITE WHERE LONG-TERM ECOLOGICAL AND BIOLOGICAL CONSEQUENCES OF A DRASTIC CHANGE IN A RANGE OF ENVIRONMENTAL FACTORS AS WELL AS TRENDS AND INTENSITY OF SELECTION ARE STUDIED IN NATURAL SETTINGS. THE CONSEQUENCES OF THE CHERNOBYL ACCIDENT FOR BIOTA VARIED FROM AN ENHANCED RATE OF MUTAGENESIS TO DAMAGE AT THE ECOSYSTEM LEVEL. THE REVIEW COMPREHENSIVELY BRINGS TOGETHER KEY DATA OF THE LONG-TERM STUDIES OF BIOLOGICAL EFFECTS IN PLANTS AND ANIMALS INHABITING OVER 20 YEARS THE CHERNOBYL NPP ZONE. THE SEVERITY OF RADIATION EFFECTS WAS STRONGLY DEPENDENT ON THE DOSE RECEIVED IN THE EARLY PERIOD AFTER THE ACCIDENT. THE MOST EXPOSED PHYTOCENOSES AND SOIL ANIMALS' COMMUNITIES EXHIBITED DOSE DEPENDENT ALTERATIONS IN THE SPECIES COMPOSITION AND REDUCTION IN BIOLOGICAL DIVERSITY. ON THE OTHER HAND, NO DECREASE IN NUMBERS OR TAXONOMIC DIVERSITY OF SMALL MAMMALS EVEN IN THE MOST RADIOACTIVE HABITAT WAS SHOWN. IN A MAJORITY OF THE STUDIES, IN BOTH PLANT AND ANIMAL POPULATIONS FROM THE CHERNOBYL ZONE, IN THE FIRST YEARS AFTER THE ACCIDENT HIGH INCREASES IN MUTATION RATES WERE DOCUMENTED. IN MOST CASES THE DOSE-EFFECT RELATIONSHIPS WERE NONLINEAR AND THE MUTATION RATES PER UNIT DOSE WERE HIGHER AT LOW DOSES AND DOSE RATES. IN SUBSEQUENT YEARS A DECLINE IN THE RADIATION BACKGROUND RATE OCCURRED FASTER THAN REDUCTION IN THE MUTATION RATE. PLANT AND ANIMAL POPULATIONS HAVE SHOWN SIGNS OF ADAPTATION TO CHRONIC EXPOSURE. IN ADAPTATION TO THE ENHANCED LEVEL OF EXPOSURE AN ESSENTIAL ROLE OF EPIGENETIC MECHANISMS OF GENE EXPRESSION REGULATION WAS SHOWN. BASED ON THE CHERNOBYL NPP ACCIDENT STUDIES, IN THE PRESENT REVIEW ATTEMPTS WERE MADE TO ASSESS MINIMUM DOSES AT WHICH ECOLOGICAL AND BIOLOGICAL EFFECTS WERE OBSERVED. 2008 5 1174 28 CONTRIBUTION OF TRANSPOSABLE ELEMENTS TO TRANSGENERATIONAL EFFECTS OF CHRONIC RADIOACTIVE EXPOSURE OF NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER LIVING FOR A LONG TIME IN THE ZONE OF THE CHERNOBYL NUCLEAR DISASTER. THE ACCIDENT AT THE CHERNOBYL NUCLEAR POWER PLANT (CHNPP) LED TO THE NEGATIVE IMPACT OF CHRONIC RADIOACTIVE CONTAMINATION ON POPULATIONS OF ORGANISMS ASSOCIATED WITH THE TRANSGENERATIONAL TRANSMISSION OF GENOME INSTABILITY. WHEN THE DESTABILIZATION OF GENOME, DIFFERENT GENETIC DAMAGES OCCUR, THE ACCUMULATION OF WHICH LEADS TO THE FORMATION OF MUTATIONS, MORPHOLOGICAL ANOMALIES, AND MORTALITY IN THE OFFSPRING. THE MECHANISMS UNDERLYING THE MANIFESTATION OF TRANSGENERATIONAL EVENTS IN THE OFFSPRING OF IRRADIATED PARENTS ARE NOT WELL UNDERSTOOD. IN THIS STUDY, FOR THE FIRST TIME, THE FEATURES OF THE INFLUENCE OF TRANSPOSABLE ELEMENTS (TES) ON THE LONG-TERM BIOLOGICAL CONSEQUENCES OF THE CHNPP ARE CONSIDERED. IN THIS WORK, SPECIMENS OF D. MELANOGASTER OBTAINED FROM NATURAL POPULATIONS IN 2007 IN THE AREAS OF THE CHNPP WITH HETEROGENEOUS RADIOACTIVE CONTAMINATION WERE STUDIED. THE DESCENDANTS FROM THESE POPULATIONS WERE MAINTAINED IN LABORATORY (INBRED) CONDITIONS FOR 160 GENERATIONS. A STABLE TRANSGENERATIONAL TRANSMISSION OF DOMINANT LETHAL MUTATIONS (DLMS) TO THE OFFSPRING OF ALL STUDIED POPULATIONS WAS SHOWN. THE DLM FREQUENCIES STRONGLY WERE CORRELATED WITH THE LEVEL OF SURVIVAL OF OFFSPRING. THE MEAN FREQUENCIES OF RECESSIVE SEX-LINKED LETHAL MUTATIONS VARIED AT THE LEVEL OF SPONTANEOUS POINT MUTATIONS. THE SIMULTANEOUS PRESENCE OF P, HOBO AND I ELEMENTS INDICATES THAT THE STUDIED POPULATIONS DO NOT HAVE A DEFINITE CYTOTYPE, THEIR PHENOTYPIC STATUS IS UNSTABLE. THE BEHAVIOR OF TES IN THE GENOMES OF OFFSPRING DEPENDS NOT ONLY ON PARENTAL EXPOSURE, BUT ALSO ON ORIGIN OF POPULATION, DISTANCE TO THE CHNPP, AND INBRED CONDITIONS. THE OBTAINED RESULTS CONFIRM THE HYPOTHESIS THAT TES ARE INVOLVED IN TRANSGENERATIONAL TRANSMISSION AND ACCUMULATION OF MUTATIONS BY THE OFFSPRING OF IRRADIATED PARENTS. THE TES PATTERN PRESENT IN THE CHERNOBYL GENOMES OF D. MELANOGASTER IS A PECULIAR OF EPIGENETIC MECHANISM FOR THE REGULATION OF PLASTICITY AND ADAPTATION OF POPULATIONS LIVING FOR MANY GENERATIONS UNDER CONDITIONS OF A TECHNOGENICALLY CAUSED RADIATION BACKGROUND. 2022 6 5344 30 RADIOBIOLOGICAL FEATURES IN OFFSPRING OF NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER AFTER CHERNOBYL ACCIDENT. IN THEIR NATURAL HABITATS, POPULATIONS OF ORGANISMS ARE FACED WITH DIFFERENT LEVELS OF CHRONIC LOW-INTENSITY RADIATION, CAUSING A WIDE RANGE OF RADIOBIOLOGICAL EFFECTS (FROM RADIOSENSITIVITY TO RADIOADAPTIVE RESPONSE AND HORMESIS). IN THIS STUDY, SPECIMENS OF DROSOPHILA MELANOGASTER WERE SELECTED FROM TERRITORIES OF THE CHERNOBYL NUCLEAR POWER PLANT WITH DIFFERENT LEVELS OF RADIOACTIVE CONTAMINATION. THE ISOGENIC STOCKS DERIVED FROM THESE SPECIMENS REPRESENT THE GENETIC SYSTEMS OF CURRENT POPULATIONS AND MAKE IT POSSIBLE TO STUDY RADIORESISTANCE AND ITS MECHANISMS IN FUTURE GENERATIONS UNDER CONTROLLED LABORATORY CONDITIONS. PREVIOUS STUDIES HAVE SHOWN THAT TRANSGENERATIONAL RADIATION EFFECTS AT THE LEVEL OF LETHAL MUTATIONS AND SURVIVAL RATE ARE UNSTABLE AND DEPEND NOT ONLY ON THE LEVEL OF CHRONIC LOW-INTENSITY IRRADIATION, BUT ALSO ON OTHER FACTORS. A SINGLE ACUTE IRRADIATION EXPOSURE OF OFFSPRING WHOSE PARENTS INHABITED A SITE WITH A HIGHER LEVEL OF CHRONIC IRRADIATION MADE IT POSSIBLE TO REVEAL PRONOUNCED RADIORESISTANT FEATURES IN THE OFFSPRING. AND THE OFFSPRING WHOSE PARENTS WERE EXPOSED TO RADIATION LEVELS CLOSE TO THE NATURAL RADIATION BACKGROUND, ON THE CONTRARY, ACQUIRED RADIOSENSITIVE FEATURES. THEIR RESPONSE TO ACUTE EXPOSURE INCLUDES A HIGH-FREQUENCY OF LETHAL MUTATIONS AND A SHORT LIFESPAN. THE DIFFERENTIAL RESPONSE TO DIFFERENT LEVELS OF CHRONIC PARENTAL EXPOSURE IS CAUSED BY DIFFERENCES IN THE ACTIVITIES OF CERTAIN TRANSPOSONS THAT DESTABILIZE THE GENOME. OUR DATA CONTRIBUTE TO THE UNDERSTANDING OF GENETIC AND EPIGENETIC MECHANISMS (VIA TRANSPOSON ACTIVITY) OF THE EFFECT OF PARENTAL RADIATION EXPOSURE ON THE HEALTH AND ADAPTIVE POTENTIAL OF POPULATIONS AFFECTED BY THE TECHNOGENICALLY INCREASED RADIATION BACKGROUND. 2022 7 6550 27 TRANSGENERATIONAL ACCUMULATION OF RADIATION DAMAGE IN SMALL MAMMALS CHRONICALLY EXPOSED TO CHERNOBYL FALLOUT. THE PURPOSE OF THIS INVESTIGATION HAS BEEN THE ANALYSIS OF THE LONG-TERM DEVELOPMENT OF BIOLOGICAL DAMAGE IN NATURAL POPULATIONS OF A MODEL MAMMALIAN SPECIES, THE BANK VOLE (CLETHRIONOMYS GLAREOLUS, SCHREBER), WHICH WERE CHRONICALLY EXPOSED TO LOW DOSES OF IONIZING RADIATION OVER 22 ANIMAL GENERATIONS WITHIN 10 YEARS FOLLOWING THE CHERNOBYL ACCIDENT. THE TIME COURSE OF THE BIOLOGICAL END-POINTS (CHROMOSOME ABERRATIONS IN BONE MARROW CELLS AND EMBRYONIC LETHALITY) WAS COMPARED WITH THE TIME COURSE OF THE WHOLE-BODY ABSORBED DOSE RATE FROM EXTERNAL AND INTERNAL EXPOSURE IN THE STUDIED POPULATIONS INHABITING MONITORING SITES IN BELARUS WITH DIFFERENT GROUND DEPOSITION OF RADIONUCLIDES. THE YIELD OF CHROMOSOME ABERRATIONS AND, IN LESSER DEGREE, EMBRYONIC LETHALITY WAS ASSOCIATED WITH THE RADIONUCLIDE CONTAMINATION OF THE MONITORING AREAS IN A DOSE-DEPENDENT MANNER. AS A MAIN FEATURE OF THE LONG-TERM DEVELOPMENT OF BIOLOGICAL DAMAGE UNDER LOW DOSE RATE IRRADIATION, PERMANENTLY ELEVATED LEVELS OF CHROMOSOME ABERRATIONS AND AN INCREASING FREQUENCY OF EMBRYONIC LETHALITY HAVE DEVELOPED OVER 22 ANIMAL GENERATIONS. THIS CONTRASTS WITH THE ASSUMPTION THAT THE BIOLOGICAL DAMAGE WOULD GRADUALLY DISAPPEAR SINCE IN THE SAME PERIOD OF TIME THE WHOLE-BODY ABSORBED DOSE RATE DECREASED EXPONENTIALLY WITH A HALF-VALUE TIME OF ABOUT 2.5-3 YEARS. FURTHERMORE, GRAVID FEMALES WERE CAPTURED, AND THEIR OFFSPRING, BORN AND GROWN UP UNDER CONTAMINATION-FREE LABORATORY CONDITIONS, SHOWED THE SAME ENHANCED LEVEL OF CHROMOSOME ABERRATIONS. THEREFORE THE AUTHORS SUGGEST THAT, ALONG WITH THE BIOLOGICAL DAMAGE ATTRIBUTABLE TO THE INDIVIDUAL EXPOSURE OF EACH ANIMAL, THE OBSERVED CELLULAR AND SYSTEMIC EFFECTS REFLECT THE TRANSGENERATIONAL TRANSMISSION AND ACCUMULATION, VIA GENETIC AND/OR EPIGENETIC PATHWAYS, OF DAMAGE ATTRIBUTABLE TO THE CHRONIC LOW-DOSE RATE EXPOSURE OF THE PRECEDING GENERATIONS OF ANIMALS. THEY ALSO SUGGEST THAT THE LEVEL OF THE ACCUMULATED TRANSMISSIBLE DAMAGE IN THE INVESTIGATED POPULATIONS WILL DECREASE IN FUTURE DUE TO THE FURTHER RECESSION OF THE CHRONIC EXPOSURE AND AS A CONSEQUENCE OF SELECTION PROCESSES. 2006 8 5342 20 RADIATION-INDUCED LATE EFFECTS IN TWO AFFECTED INDIVIDUALS OF THE LILO RADIATION ACCIDENT. RADIATION EXPOSURE LEADS TO A RISK FOR LONG-TERM DETERMINISTIC AND STOCHASTIC LATE EFFECTS. TWO INDIVIDUALS EXPOSED TO PROTRACTED PHOTON RADIATION IN THE RADIOLOGICAL ACCIDENT AT THE LILO MILITARY SITE IN GEORGIA IN 1997 RECEIVED FOLLOW-UP TREATMENT AND RESECTION OF SEVERAL CHRONIC RADIATION ULCERS IN THE BUNDESWEHR HOSPITAL ULM, GERMANY, IN 2003. MULTI-PARAMETER ANALYSIS REVEALED THAT SPERMATOGENETIC ARREST AND SERUM HORMONE LEVELS IN BOTH PATIENTS HAD RECOVERED COMPARED TO THE STATUS IN 1997. HOWEVER, WE OBSERVED A PERSISTENCE OF ALTERED T-CELL RATIOS, INCREASED ICAM1 AND BETA1-INTEGRIN EXPRESSION, AND ABERRANT BONE MARROW CELLS AND LYMPHOCYTES WITH SIGNIFICANTLY INCREASED TRANSLOCATIONS 6 YEARS AFTER THE ACCIDENT. THIS INVESTIGATION THUS IDENTIFIED ALTERED END POINTS STILL DETECTABLE YEARS AFTER THE ACCIDENT THAT SUGGEST PERSISTENT GENOMIC DAMAGE AS WELL AS EPIGENETIC EFFECTS IN THESE INDIVIDUALS, WHICH MAY BE ASSOCIATED WITH AN ELEVATED RISK FOR THE DEVELOPMENT OF FURTHER LATE EFFECTS. OUR OBSERVATIONS FURTHER SUGGEST THE DEVELOPMENT OF A CHRONIC RADIATION SYNDROME AND INDICATE FOLLOW-UP PARAMETERS IN RADIATION VICTIMS. 2007 9 1325 19 DEPLETED URANIUM INDUCES SEX- AND TISSUE-SPECIFIC METHYLATION PATTERNS IN ADULT ZEBRAFISH. WE EXAMINED THE EFFECTS OF CHRONIC EXPOSURE TO DIFFERENT CONCENTRATIONS (2 AND 20 MUG L(-)(1)) OF ENVIRONMENTALLY RELEVANT WATERBORNE DEPLETED URANIUM (DU) ON THE DNA METHYLATION PATTERNS BOTH AT HPAII RESTRICTION SITES (5'-CCGG-3') AND ACROSS THE WHOLE GENOME IN THE ZEBRAFISH BRAIN, GONADS, AND EYES. WE FIRST IDENTIFIED SEX-DEPENDENT DIFFERENCES IN THE METHYLATION LEVEL OF HPAII SITES AFTER EXPOSURE. IN MALES, THESE EFFECTS WERE PRESENT AS EARLY AS 7 DAYS AFTER EXPOSURE TO 20 MUG L(-)(1) DU, AND WERE EVEN MORE PRONOUNCED IN THE BRAIN, GONADS, AND EYES AFTER 24 DAYS. HOWEVER, IN FEMALES, HYPOMETHYLATION WAS ONLY OBSERVED IN THE GONADS AFTER EXPOSURE TO 20 MUG L(-)(1) DU FOR 24 DAYS. SEX-SPECIFIC EFFECTS OF DU WERE ALSO APPARENT AT THE WHOLE-GENOME LEVEL, BECAUSE IN MALES, EXPOSURE TO 20 MUG L(-)(1) DU FOR 24 DAYS RESULTED IN CYTOSINE HYPERMETHYLATION IN THE BRAIN AND EYES AND HYPOMETHYLATION IN THE GONADS. IN CONTRAST, IN FEMALES, HYPERMETHYLATION WAS OBSERVED IN THE BRAIN AFTER EXPOSURE TO BOTH CONCENTRATIONS OF DU FOR 7 DAYS. BASED ON OUR CURRENT KNOWLEDGE OF URANIUM TOXICITY, SEVERAL HYPOTHESES ARE PROPOSED TO EXPLAIN THESE FINDINGS, INCLUDING THE INVOLVEMENT OF OXIDATIVE STRESS, ALTERATION OF DEMETHYLATION ENZYMES AND THE CALCIUM SIGNALING PATHWAY. THIS STUDY REPORTS, FOR THE FIRST TIME, THE SEX- AND TISSUE-SPECIFIC EPIGENETIC CHANGES THAT OCCUR IN A NONHUMAN ORGANISM AFTER EXPOSURE TO ENVIRONMENTALLY RELEVANT CONCENTRATIONS OF URANIUM, WHICH COULD INDUCE TRANSGENERATIONAL EPIGENETIC EFFECTS. 2016 10 6673 20 USE OF COMPUTER TV MORPHODENSITOMETRY TO STUDY EPIGENETIC CHANGES IN BLOOD LYMPHOCYTES FROM CHILDREN AFFECTED BY LOW-DOSE IRRADIATION. A NOVEL METHOD, COMPUTER TV MORPHODENSITOMETRY, WAS USED TO EVALUATE THE EFFECTS OF LOW-DOSE IRRADIATION ON PERIPHERAL BLOOD LYMPHOCYTES FROM CHILDREN AFFECTED BY THE CHERNOBYL DISASTER. THIS METHOD USES DIGITIZED IMAGES TO DETECT AND MEASURE CHANGES IN CHROMATIN SHAPE AND DENSITY AND TO PRODUCE TWO-DIMENSIONAL AND THREE-DIMENSIONAL PICTURES. IMAGES CAN THEN BE STORED TO CREATE A VIDEO ARCHIVE. THIS METHOD IS SENSITIVE ENOUGH TO OBSERVE SUBTLE CHANGES IN CHROMATIN STRUCTURE THAT PREVIOUSLY COULD BE DETECTED ONLY BY MORE DETAILED MOLECULAR ANALYSES. IN THIS STUDY, LYMPHOCYTE INTERPHASE NUCLEI IN DNA-STAINED BLOOD SMEARS FROM CHILDREN SUBJECTED TO CHRONIC LOW-DOSE IRRADIATION WERE EXAMINED BY COMPUTER TV MORPHODENSITOMETRY. PRELIMINARY DATA INDICATE THAT CIRCULATING LYMPHOCYTES FROM CHILDREN EXPOSED TO RADIATION MAY CONTAIN SIGNIFICANT ALTERATIONS IN THE STRUCTURE AND/OR DENSITY OF NUCLEAR CHROMATIN. 1997 11 5032 22 PERTURBED TRANSCRIPTIONAL PROFILES AFTER CHRONIC LOW DOSE RATE RADIATION IN MICE. ADVERSE HEALTH OUTCOMES OF IONIZING RADIATION GIVEN CHRONICALLY AT LOW DOSE RATES ARE HIGHLY DEBATED, A CONTROVERSY ALSO RELEVANT FOR OTHER STRESSORS. INCREASED KNOWLEDGE IS NEEDED FOR A MORE COMPREHENSIVE UNDERSTANDING OF THE DAMAGING POTENTIAL OF IONIZING RADIATION FROM ALL DOSE RATES AND DOSES. THERE IS A LACK OF RELEVANT LOW DOSE RATE DATA THAT IS PARTLY ASCRIBED TO THE RARITY OF EXPOSURE FACILITIES ALLOWING CHRONIC LOW DOSE RATE EXPOSURES. USING THE FIGARO FACILITY, WE ASSESSED EARLY (ONE DAY POST-RADIATION) AND LATE (RECOVERY TIME OF 100-200 DAYS) HEPATIC GENOME-WIDE TRANSCRIPTIONAL PROFILES IN MALE MICE OF TWO STRAINS (CBA/CAOLAHSD AND C57BL/6NHSD) EXPOSED CHRONICALLY TO A LOW DOSE RATE (2.5 MGY/H; 1200H, LDR), A MID-DOSE RATE (10 MGY/H; 300H, MDR) AND ACUTELY TO A HIGH DOSE RATE (100 MGY/H; 30H, HDR) OF GAMMA IRRADIATION, GIVEN TO AN EQUIVALENT TOTAL DOSE OF 3 GY. DOSE-RATE AND STRAIN-SPECIFIC TRANSCRIPTIONAL RESPONSES WERE IDENTIFIED. DIFFERENTLY MODULATED TRANSCRIPTIONAL RESPONSES ACROSS ALL DOSE RATE EXPOSURE GROUPS WERE EVIDENT BY THE REPRESENTATION OF FUNCTIONAL BIOLOGICAL PATHWAYS. EVIDENCE OF CHANGED EPIGENETIC REGULATION (GLOBAL DNA METHYLATION) WAS NOT DETECTED. A PERIOD OF RECOVERY MARKEDLY REDUCED THE NUMBER OF DIFFERENTIALLY EXPRESSED GENES. USING ENRICHMENT ANALYSIS TO IDENTIFY THE FUNCTIONAL SIGNIFICANCE OF THE MODULATED GENES, PERTURBED SIGNALING PATHWAYS ASSOCIATED WITH BOTH CANCER AND NON-CANCER EFFECTS WERE OBSERVED, SUCH AS LIPID METABOLISM AND INFLAMMATION. THESE PATHWAYS WERE SEEN AFTER CHRONIC LOW DOSE RATE AND WERE NOT RESTRICTED TO THE ACUTE HIGH DOSE RATE EXPOSURE. THE TRANSCRIPTIONAL RESPONSE INDUCED BY CHRONIC LOW DOSE RATE IONIZING RADIATION SUGGESTS CONTRIBUTION TO CONDITIONS SUCH AS CARDIOVASCULAR DISEASES. WE CONTRIBUTE WITH NOVEL GENOME WIDE TRANSCRIPTIONAL DATA HIGHLIGHTING DOSE-RATE-SPECIFIC RADIATION RESPONSES AND EMPHASIZE THE IMPORTANCE OF CONSIDERING BOTH DOSE RATE, DURATION OF EXPOSURE, AND VARIABILITY IN SUSCEPTIBILITY WHEN ASSESSING RISKS FROM IONIZING RADIATION. 2021 12 6552 20 TRANSGENERATIONAL DNA METHYLATION CHANGES IN DAPHNIA MAGNA EXPOSED TO CHRONIC GAMMA IRRADIATION. OUR AIM WAS TO INVESTIGATE EPIGENETIC CHANGES IN DAPHNIA MAGNA AFTER A 25-DAY CHRONIC EXTERNAL GAMMA IRRADIATION (GENERATION F0 EXPOSED TO 6.5 MUGY.H(-1) OR 41.3 MGY.H(-1)) AND THEIR POTENTIAL INHERITANCE BY SUBSEQUENT RECOVERING GENERATIONS, NAMELY, F2 (EXPOSED AS GERMLINE CELLS IN F1 EMBRYOS) AND F3 (THE FIRST TRULY UNEXPOSED GENERATION). EFFECTS ON SURVIVAL, GROWTH, AND REPRODUCTION WERE OBSERVED AND DNA WAS EXTRACTED FOR WHOLE-GENOME BISULFITE SEQUENCING IN ALL GENERATIONS. RESULTS SHOWED EFFECTS ON REPRODUCTION IN F0 BUT NO EFFECT IN THE SUBSEQUENT GENERATIONS F1, F2, AND F3. IN CONTRAST, WE OBSERVED SIGNIFICANT METHYLATION CHANGES AT SPECIFIC CPG POSITIONS IN EVERY GENERATION INDEPENDENT OF DOSE RATE, WITH A MAJORITY OF HYPOMETHYLATION. SOME OF THESE CHANGES WERE SHARED BETWEEN DOSE RATES AND BETWEEN GENERATIONS. ASSOCIATED GENE FUNCTIONS INCLUDED GENE FAMILIES AND GENES THAT WERE PREVIOUSLY SHOWN TO PLAY ROLES DURING EXPOSURE TO IONIZING RADIATION. COMMON METHYLATION CHANGES DETECTED BETWEEN GENERATIONS F2 AND F3 CLEARLY SHOWED THAT EPIGENETIC MODIFICATIONS CAN BE TRANSMITTED TO UNEXPOSED GENERATIONS, MOST LIKELY THROUGH THE GERMLINE, WITH POTENTIAL IMPLICATIONS FOR ENVIRONMENTAL RISK. 2018 13 4528 13 MULTIGENERATIONAL EFFECTS OF CADMIUM ON THE LIFESPAN AND FERTILITY OF DROSOPHILA MELANOGASTER. ALTHOUGH THE DAMAGE AND TOLERANCE MECHANISMS OF CD STRESS ARE KNOWN, THE DATA ON GENETIC RISK ARE LIMITED. THE AIM OF THIS STUDY WAS TO ASSESS THE CHRONIC TOXICITY OF CD, GENETIC RESPONSES, AND MULTIGENERATIONAL EFFECTS IN FIVE GENERATIONS OF DROSOPHILA MELANOGASTER. FOR EACH GENERATION, LIFESPAN AND FERTILITY WERE STATISTICALLY ANALYSED AND THE EXPRESSION OF APOPTOSIS- (P53 AND CASPASE-3) AND EPIGENESIS-RELATED (DDNMT2 AND DMBD2/3) GENES WAS EXAMINED. LIFESPAN AND FERTILITY SIGNIFICANTLY DECLINED UNDER CD STRESS AND THESE EFFECTS WERE MAINTAINED FOR TWO GENERATIONS AND ONE GENERATION, RESPECTIVELY, WHEN CD STRESS WAS REMOVED. THE EXPRESSION OF P53 AND CASPASE-3 WAS SIGNIFICANTLY UP-REGULATED AFTER EXPOSURE, SUGGESTING THAT APOPTOSIS CONTRIBUTES TO THE RESISTANCE MECHANISM. THEIR ALTERED EXPRESSION WAS RETAINED FOR TWO GENERATIONS. FURTHERMORE, HIGH EXPRESSION OF DDNMT2 AND DMBD2/3 ACCOMPANIED CD EXPOSURE, WHICH WAS PASSED ON TO THREE GENERATIONS, SUGGESTING THAT GENETIC MODIFICATIONS IN APOPTOSIS-RELATED GENES ARE CARRIED TO THE OFFSPRING THROUGH EPIGENETIC REGULATION. 2020 14 6555 23 TRANSGENERATIONAL EFFECTS OF GAMMA RADIATION DOSE AND DOSE RATE ON DROSOPHILA FLIES IRRADIATED AT AN EARLY EMBRYONAL STAGE. IONIZING RADIATION (IR) KILLS CELLS MAINLY THROUGH INDUCTION OF DNA DAMAGES AND THE SURVIVING CELLS MAY SUFFER FROM MUTATIONS. TRANSGENERATIONAL EFFECTS OF IR ARE WELL DOCUMENTED, BUT THE EXACT MECHANISMS UNDERLYING THEM ARE LESS WELL UNDERSTOOD; THEY INCLUDE INDUCTION OF MUTATIONS IN GERM CELLS AND EPIGENETIC INHERITANCE. PREVIOUSLY, EFFECTS IN THE OFFSPRING OF MICE AND ZEBRAFISH EXPOSED TO IR HAVE BEEN REPORTED. A FEW STUDIES ALSO SHOWED INDICATIONS OF TRANSGENERATIONAL EFFECTS OF RADIATION IN HUMANS, PARTICULARLY IN NUCLEAR POWER WORKERS. IN THE PRESENT PROJECT, SHORT- AND LONG-TERM EFFECTS OF LOW-DOSE-RATE (LDR; 50 AND 97 MGY/H) AND HIGH-DOSE-RATE (HDR; 23.4, 47.1 AND 495 GY/H) IR IN DROSOPHILA EMBRYOS WERE INVESTIGATED. THE EMBRYOS WERE IRRADIATED AT DIFFERENT DOSES AND DOSE RATES AND RADIOSENSITIVITY AT DIFFERENT DEVELOPMENTAL STAGES WAS INVESTIGATED. ALSO, THE SURVIVAL OF LARVAE, PUPAE AND ADULTS DEVELOPED FROM EMBRYOS IRRADIATED AT AN EARLY STAGE (30 MIN AFTER EGG LAYING) WERE STUDIED. THE LARVAL CRAWLING AND PUPATION HEIGHT ASSAYS WERE APPLIED TO INVESTIGATE RADIATION EFFECTS ON LARVAL LOCOMOTION AND PUPATION BEHAVIOR, RESPECTIVELY. IN PARALLEL, THE OFFSPRING FROM 3 GY IRRADIATED EARLY-STAGE EMBRYOS WERE FOLLOWED UP TO 12 GENERATIONS AND ABNORMAL PHENOTYPES WERE STUDIED. ACUTE EXPOSURE OF EMBRYOS AT DIFFERENT STAGES OF DEVELOPMENT SHOWED THAT THE EARLY STAGE EMBRYO IS THE MOST SENSITIVE. THE EFFECTS ON LARVAL LOCOMOTION SHOWED NO SIGNIFICANT DIFFERENCES BETWEEN THE DOSE RATES BUT A SIGNIFICANT DECREASE OF LOCOMOTION ACTIVITY ABOVE 7 GY WAS OBSERVED. THE RESULTS INDICATE THAT EMBRYOS EXPOSED TO THE LOW DOSE RATES HAVE SHORTER ECLOSION TIMES. AT THE SAME CUMULATIVE DOSE (1 UP TO 7 GY), HDR IS MORE EMBRYOTOXIC THAN LDR. WE ALSO FOUND A RADIATION-INDUCED DEPIGMENTATION ON MALES (A5 SEGMENT OF THE DORSAL ABDOMEN, A5PIG(-)) THAT CAN BE TRANSMITTED UP TO 12 GENERATIONS. THE PHENOMENON DOES NOT FOLLOW THE CLASSICAL MENDELIAN LAWS OF SEGREGATION. 2022 15 903 15 CHRONIC EXPOSURE TO BISPHENOL A RESULTED IN ALTERATIONS OF REPRODUCTIVE FUNCTIONS VIA IMMUNE DEFENSE, OXIDATIVE DAMAGE AND DISRUPTION DNA/HISTONE METHYLATION IN MALE RARE MINNOW GOBIOCYPRIS RARUS. BISPHENOL A (BPA) IS A WIDELY USED CHEMICAL THAT REPRESENTS A REPRODUCTIVE HAZARD IN FISH. HOWEVER, THE MOLECULAR PATHWAYS MEDIATING REPRODUCTIVE TOXICITY UNDER CHRONIC BPA EXPOSURE REMAIN UNCLEAR. TO STUDY THE REPRODUCTIVE HAZARDS ASSOCIATED WITH CHRONIC BPA EXPOSURE, ADULT MALE RARE MINNOWS (GOBIOCYPRIS RARUS) WERE TREATED WITH 15 MUG L (-) (1) AND 225 MUG L (-) (1) BPA FOR 90 DAYS. RESULTS SHOWED THAT CHRONIC BPA TREATMENT INDUCED REPRODUCTIVE IMPAIRMENTS WITH DECREASED FERTILIZATION CAPACITY AND MOVEMENT TIME OF SPERM. TRANSCRIPTOME ANALYSIS INDICATED 1421 TRANSCRIPTS THAT WERE DIFFERENTIALLY EXPRESSED IN RESPONSE TO BPA EXPOSURE, WHICH ARE INVOLVED IN THE BIOLOGICAL PROCESS OF OXIDATIVE STRESS, IMMUNE RESPONSES AND DNA/HISTONE METHYLATION. BPA CAUSED THE OXIDATIVE STRESS VIA SIGNIFICANTLY INCREASING HYDROGEN PEROXIDE (H(2)O(2)) LEVELS AND INHIBITING THE ACTIVITIES OF ANTIOXIDANT-RELATED ENZYMES (CATALASE, CAT). BPA CAUSED AN INFLAMMATORY RESPONSE IN THE TESTES BY SIGNIFICANTLY INCREASING IL-1BETA LEVELS AND INDUCING INFILTRATION OF INFLAMMATORY CELLS. MOREOVER, EXPOSURE TO 15 MUG L (-) (1) BPA SIGNIFICANTLY DECREASED THE GENOMIC DNA METHYLATION LEVEL. THESE DATA REVEALED THAT CHRONIC BPA EXPOSURE HAD ADVERSE EFFECTS ON MALE REPRODUCTION. OXIDATIVE STRESS, INFLAMMATORY RESPONSE AND DNA/HISTONE METHYLATION MIGHT ACCOUNT FOR THE DECREASED SPERM QUALITY. 2021 16 6845 22 [METHYLATION STATUS OF APOPTOSIS GENES AND INTENSITY OF APOPTOTIC DEATH OF PERIPHERAL BLOOD LYMPHOCYTES IN PERSONS CHRONICALLY EXPOSED TO RADIATION]. METHYLATION OF THE CPG ISLANDS OF GENE PROMOTER REGIONS IS THE MOST COMMON EPIGENETIC MODIFICATION INVOLVED IN THE REGULATION OF GENE EXPRESSION. A NUMBER OF STUDIES HAVE SHOWN THAT IONIZING RADIATION CAN CAUSE BOTH HYPER- AND HYPOMETHYLATION OF DNA. ABERRANT METHYLATION AFFECTS CELLULAR PROCESSES AND CAN LEAD TO THE DEVELOPMENT OF VARIOUS PATHOLOGICAL STATES. IN THE LITERATURE, THERE ARE FEW STUDIES ON THE METHYLATION STATUS OF HUMAN DNA A LONG TIME AFTER RADIATION EXPOSURE. HERE, THE METHYLATION LEVEL OF CPG ISLANDS OF THE PROMOTER REGIONS OF APOPTOSIS GENES (BCL2, ATM, MDM2, CDKN1A, STAT3, AND NFKB1), AND ALSO ITS INFLUENCE ON APOPTOSIS OF PERIPHERAL BLOOD LYMPHOCYTES IN CHRONICALLY EXPOSED PERSONS WERE STUDIED. RESIDENTS OF THE SOUTH URAL REGION WHO WERE CHRONICALLY EXPOSED TO RADIATION (AFTER DISCHARGES OF RADIOACTIVE WASTES INTO THE TECHA RIVER BY THE "MAYAK PRODUCTION ASSOCIATION" IN 1949-1956) WERE INCLUDED IN THE STUDY. IT WAS ESTABLISHED THAT THE PROPORTION OF INDIVIDUALS WITH HYPERMETHYLATED BCL2 GENE PROMOTER AMONG THE EXPOSED PEOPLE WAS STATISTICALLY SIGNIFICANTLY HIGHER THAN IN THE CONTROL GROUP. THE PERCENTAGE OF METHYLATION OF THE ATM GENE PROMOTER WEAKLY POSITIVELY CORRELATED WITH DOSE AND AGE CHARACTERISTICS. DIFFERENCES IN THE FREQUENCY OF LYMPHOCYTE APOPTOSIS IN EXPOSED INDIVIDUALS WITH A HYPO- OR HYPERMETHYLATED ATM GENE PROMOTER WERE ALSO ESTABLISHED. THE DATA INDICATE THAT, IN THE LONG-TERM, AFTER CHRONIC LOW INTENSITY RADIATION EXPOSURE AT LOW AND MEDIUM DOSES, EPIGENETIC MODIFICATIONS OF THE GENOME OCCUR, WHICH ARE MANIFESTED AS CHANGES IN METHYLATION OF PROMOTER REGIONS OF BCL2 AND ATM GENES. 2022 17 6794 19 [EFFECT OF BENZO(A)PYRENE ON THE EXPRESSION OF AHR-REGULATED MICRORNA IN FEMALE AND MALE RAT LUNGS]. SMOKING IS THE MAIN RISK FACTOR FOR LUNG CANCER, MAINLY DUE TO PRESENCE OF NITROSAMINES AND POLYCYCLIC AROMATIC HYDROCARBONS, INCLUDING BENZO[A]PYRENE (BP) IN TOBACCO SMOKE COMPOSITION. THE GENOTOXIC EFFECT OF BP IS BASED ON THE HIGH DNA-BINDING ABILITY OF ITS METABOLITES, WHILE THE EPIGENETIC EFFECTS ARE MEDIATED BY A CHANGE IN THE EXPRESSION OF CANCER RELATED GENES OR REGULATORY RNAS. IT HAS BEEN SHOWN THAT WOMEN HAVE A HIGHER RISK TO DEVELOP LUNG CANCER UPON SMOKING RATHER THAN MEN. WE HYPOTHESIZED THAT CROSSTALK BETWEEN SIGNALING PATHWAYS ACTIVATED BY BP AND ESTROGENS COULD UNDERLIE THE SEX-DEPENDENT DIFFERENCES IN MIRNAS EXPRESSION. TO TEST THIS HYPOTHESIS, MALE AND FEMALE RATS WERE SUBJECTED TO SHORT-TERM OR LONG-TERM BP EXPOSURE. USING IN SILICO ANALYSIS, MIRNAS CONTAINING THE ER- AND AHR-BINDING SITES IN THE PROMOTERS OF THE GENES (OR HOST GENES) WERE SELECTED. DURING CHRONIC EXPOSURE OF BP THE EXPRESSION OF MIR-22-3P, -29A-3P, -126A-3P, -193B-5P IN THE LUNGS OF MALE RATS WERE SIGNIFICANTLY INCREASED, WHILE THE LEVEL OF MIRNA-483-3P WERE DECREASED. EXPRESSION OF MIRNA-483-3P WAS UP-REGULATED DURING CHRONIC BP EXPOSURE IN THE LUNGS OF FEMALE RATS AND THE LEVELS OF OTHER STUDIED MIRNAS WERE UNCHANGED. IN TURN, CHANGES IN THE EXPRESSION OF MIRNAS WERE FOLLOWED BY CHANGES IN THE EXPRESSION OF THEIR TARGET GENES, INCLUDING PTEN, EMP2, IGF1, ITGA6, SLC34A2, AND THE OBSERVED CHANGES IN FEMALE AND MALE RAT LUNGS WERE VARIED. THUS, OUR RESULTS SUGGEST THAT SEX-DEPENDENT EPIGENETIC EFFECTS OF BP MAY BE BASED ON DIFFERENT EXPRESSION OF AHR- AND ER- REGULATED MIRNAS. 2020 18 1545 22 DNA METHYLATION IN LIVER TUMORIGENESIS IN FISH FROM THE ENVIRONMENT. THE LINK BETWEEN ENVIRONMENT, ALTERATION IN DNA METHYLATION AND CANCER HAS BEEN WELL ESTABLISHED IN HUMANS; YET, IT IS UNDER-STUDIED IN UNSEQUENCED NON-MODEL ORGANISMS. THE OCCURRENCE OF LIVER TUMORS IN THE FLATFISH DAB COLLECTED AT CERTAIN UK SAMPLING SITES EXCEEDS 20%, YET THE CAUSATIVE AGENTS AND THE MOLECULAR MECHANISMS OF TUMOR FORMATION ARE NOT KNOWN, ESPECIALLY REGARDING THE BALANCE BETWEEN EPIGENETIC AND GENETIC FACTORS. METHYLATED DNA IMMUNOPRECIPITATION (MEDIP) COMBINED WITH DE NOVO HIGH-THROUGHPUT DNA SEQUENCING WERE USED TO INVESTIGATE DNA METHYLATION CHANGES IN DAB HEPATOCELLULAR ADENOMA TUMORS FOR THE FIRST TIME IN AN UNSEQUENCED SPECIES. NOVEL CUSTOM-MADE DAB GENE EXPRESSION ARRAYS WERE DESIGNED AND USED TO DETERMINE THE RELATIONSHIP BETWEEN DNA METHYLATION AND GENE EXPRESSION. IN ADDITION, THE CONFIRMATORY TECHNIQUES OF BISULFITE SEQUENCING PCR (BSP) AND RT-PCR WERE APPLIED. GENES INVOLVED IN PATHWAYS RELATED TO CANCER, INCLUDING APOPTOSIS, WNT/BETA-CATENIN SIGNALING AND GENOMIC AND NON-GENOMIC ESTROGEN RESPONSES, WERE ALTERED BOTH IN METHYLATION AND TRANSCRIPTION. GLOBAL METHYLATION WAS STATISTICALLY SIGNIFICANTLY 1.8-FOLD REDUCED IN HEPATOCELLULAR ADENOMA AND NON-CANCEROUS SURROUNDING TISSUES COMPARED WITH LIVER FROM NON-CANCER BEARING DAB. BASED ON THE IDENTIFIED CHANGES AND CHEMICAL EXPOSURE DATA, OUR STUDY SUPPORTS THE EPIGENETIC MODEL OF CANCER. WE HYPOTHESIZE THAT CHRONIC EXPOSURE TO A MIXTURE OF ENVIRONMENTAL CONTAMINANTS CONTRIBUTES TO A GLOBAL HYPOMETHYLATION FOLLOWED BY FURTHER EPIGENETIC AND GENOMIC CHANGES. THE FINDINGS SUGGEST A LINK BETWEEN ENVIRONMENT, EPIGENETICS AND CANCER IN FISH TUMORS IN THE WILD AND SHOW THE UTILITY OF THIS METHODOLOGY FOR STUDIES IN NON-MODEL ORGANISMS. 2011 19 1847 23 EFFECTS OF VARIOUS ENVIRONMENTS ON EPIGENETIC SETTINGS AND CHROMOSOMAL DAMAGE. AIR POLLUTION IS A DOMINANT ENVIRONMENTAL EXPOSURE FACTOR WITH SIGNIFICANT HEALTH CONSEQUENCES. UNEXPECTEDLY, RESEARCH IN A HEAVILY POLLUTED REGION OF THE CZECH REPUBLIC, WITH TRADITIONAL HEAVY INDUSTRY, REVEALED REPEATEDLY THE LOWEST FREQUENCY OF MICRONUCLEI IN THE SEASON WITH THE HIGHEST CONCENTRATIONS OF AIR POLLUTANTS INCLUDING CARCINOGENIC BENZO[A]PYRENE (B[A]P). MOLECULAR FINDINGS HAVE BEEN COLLECTED FOR MORE THAN 10 YEARS FROM VARIOUS LOCATIONS OF THE CZECH REPUBLIC, WITH DIFFERING QUALITY OF AMBIENT AIR. PRELIMINARY CONCLUSIONS HAVE SUGGESTED ADAPTATION OF THE POPULATION FROM THE POLLUTED LOCALITY (OSTRAVA, MORAVIAN-SILESIAN REGION (MSR)) TO CHRONIC AIR POLLUTION EXPOSURE. IN THIS STUDY WE UTILIZE THE PREVIOUS FINDINGS AND, FOR THE FIRST TIME, INVESTIGATE MICRONUCLEI (MN) FREQUENCY BY TYPE: (I) CENTROMERE POSITIVE (CEN+) MN, REPRESENTING CHROMOSOMAL LOSSES, AND (II) CENTROMERE NEGATIVE (CEN-) MN REPRESENTING CHROMOSOMAL BREAKS. AS PREVIOUS RESULTS INDICATED DIFFERENCES BETWEEN POPULATIONS IN THE EXPRESSION OF XRCC5, A GENE INVOLVED IN THE NON-HOMOLOGOUS END-JOINING (NHEJ) REPAIR PATHWAY, POSSIBLE VARIATIONS IN EPIGENETIC SETTINGS IN THIS GENE WERE ALSO INVESTIGATED. THIS NEW RESEARCH WAS CONDUCTED IN TWO SEASONS IN THE GROUPS FROM TWO LOCALITIES WITH DIFFERENT AIR QUALITY LEVELS (OSTRAVA (OS) AND PRAGUE (PG)). THE OBTAINED NEW RESULTS SHOW SIGNIFICANTLY LOWER FREQUENCIES OF CHROMOSOMAL BREAKS IN THE OS SUBJECTS, RELATED TO THE HIGHEST AIR POLLUTION LEVELS (P < 0.001). IN CONTRAST, CHROMOSOMAL LOSSES WERE COMPARABLE BETWEEN BOTH GROUPS. IN ADDITION, SIGNIFICANTLY LOWER DNA METHYLATION WAS FOUND IN 14.3% OF THE ANALYZED CPG LOCI OF XRCC5 IN THE POPULATION FROM OS. IN CONCLUSION, THE EPIGENETIC ADAPTATION (HYPOMETHYLATION) IN XRCC5 INVOLVED IN THE NHEJ REPAIR PATHWAY IN THE POPULATION FROM THE POLLUTED REGION, WAS SUGGESTED AS A REASON FOR THE REDUCED LEVEL OF CHROMOSOMAL BREAKS. FURTHER RESEARCH IS NEEDED TO EXPLORE THE ADDITIONAL MECHANISMS, INCLUDING GENETIC ADAPTATION. 2023 20 3991 19 LONGITUDINAL EFFECTS OF DEVELOPMENTAL BISPHENOL A, VARIABLE DIET, AND PHYSICAL ACTIVITY ON AGE-RELATED METHYLATION IN BLOOD. RESEARCH INDICATES THAT ENVIRONMENTAL FACTORS CAN ALTER DNA METHYLATION, BUT THE SPECIFIC EFFECTS OF ENVIRONMENTAL EXPOSURES ON EPIGENETIC AGING REMAIN UNCLEAR. HERE, USING A MOUSE MODEL OF HUMAN-RELEVANT EXPOSURES, WE TESTED THE HYPOTHESIS THAT EARLY-LIFE EXPOSURE TO BISPHENOL A (BPA), VARIABLE DIET, AND/OR CHANGES IN PHYSICAL ACTIVITY WOULD MODIFY RATES OF AGE-RELATED METHYLATION AT SEVERAL TARGET REGIONS, AS MEASURED FROM LONGITUDINAL BLOOD SAMPLES (2, 4, AND 10 MONTHS OLD). DNA METHYLATION WAS QUANTIFIED AT TWO REPETITIVE ELEMENTS (LINE-1, IAP), TWO IMPRINTED GENES (IGF2, H19), AND ONE NON-IMPRINTED GENE (ESR1) IN ISOGENIC MICE DEVELOPMENTALLY EXPOSED TO CONTROL, CONTROL + BPA (50 MICROG/KG DIET), WESTERN HIGH-FAT DIET (WHFD), OR WESTERN + BPA DIETS. IN BLOOD SAMPLES, ESR1 DNA METHYLATION INCREASED SIGNIFICANTLY WITH AGE, BUT NO OTHER INVESTIGATED LOCI SHOWED SIGNIFICANT AGE-RELATED METHYLATION. LINE-1 AND IAP BOTH SHOWED SIGNIFICANT NEGATIVE ENVIRONMENTAL DEFLECTION BY WHFD EXPOSURE (P < 0.05). ESR1ALSO SHOWED SIGNIFICANT NEGATIVE ENVIRONMENTAL DEFLECTION BY WHFD EXPOSURE IN FEMALE MICE (P = 0.02), BUT NOT MALE MICE. PHYSICAL ACTIVITY HAD A NON-SIGNIFICANT POSITIVE EFFECT ON AGE-RELATED ESR1 METHYLATION IN FEMALE BLOOD, SUGGESTING THAT IT MAY PARTIALLY ABROGATE THE EFFECTS OF WHFD ON THE AGING EPIGENOME. THESE RESULTS SUGGEST THAT DEVELOPMENTAL NUTRITIONAL EXPOSURES CAN MODIFY AGE-RELATED DNA METHYLATION PATTERNS AT A GENE RELATED TO GROWTH AND DEVELOPMENT. AS SUCH, ENVIRONMENTAL DEFLECTION OF THE AGING EPIGENOME MAY HELP TO EXPLAIN THE GROWING PREVALENCE OF CHRONIC DISEASES IN HUMAN POPULATIONS. 2018