1 106 116 A REVIEW OF MOLECULAR EVENTS OF CADMIUM-INDUCED CARCINOGENESIS. CADMIUM (CD) IS A TOXIC, HEAVY INDUSTRIAL METAL THAT POSES SERIOUS ENVIRONMENTAL HEALTH HAZARDS TO BOTH HUMANS AND WILDLIFE. RECENTLY, CD AND CD-CONTAINING COMPOUNDS HAVE BEEN CLASSIFIED AS KNOWN HUMAN CARCINOGENS, AND EPIDEMIOLOGICAL DATA SHOW CAUSAL ASSOCIATIONS WITH PROSTATE, BREAST, AND LUNG CANCER. THE MOLECULAR MECHANISMS INVOLVED IN CD-INDUCED CARCINOGENESIS ARE POORLY UNDERSTOOD AND ARE ONLY NOW BEGINNING TO BE ELUCIDATED. THE EFFECTS OF CHRONIC EXPOSURE TO CD HAVE RECENTLY ATTRACTED GREAT INTEREST DUE TO THE DEVELOPMENT OF MALIGNANCIES IN CD-INDUCED TUMORIGENESIS IN ANIMALS MODELS. BRIEFLY, VARIOUS IN VITRO STUDIES DEMONSTRATE THAT CD CAN ACT AS A MITOGEN, CAN STIMULATE CELL PROLIFERATION AND INHIBIT APOPTOSIS AND DNA REPAIR, AND CAN INDUCE CARCINOGENESIS IN SEVERAL MAMMALIAN TISSUES AND ORGANS. THUS, THE VARIOUS MECHANISMS INVOLVED IN CHRONIC CD EXPOSURE AND MALIGNANT TRANSFORMATIONS WARRANT FURTHER INVESTIGATION. IN THIS REVIEW, WE FOCUS ON RECENT EVIDENCE OF VARIOUS LEADING GENERAL AND TISSUE-SPECIFIC MOLECULAR MECHANISMS THAT FOLLOW CHRONIC EXPOSURE TO CD IN PROSTATE-, BREAST-, AND LUNG-TRANSFORMED MALIGNANCIES. IN ADDITION, IN THIS REVIEW, WE CONSIDER LESS DEFINED MECHANISMS SUCH AS EPIGENETIC MODIFICATION AND AUTOPHAGY, WHICH ARE THOUGHT TO PLAY A ROLE IN THE DEVELOPMENT OF CD-INDUCED MALIGNANT TRANSFORMATION. 2014 2 3739 49 INS AND OUTS OF CADMIUM-INDUCED CARCINOGENESIS: MECHANISM AND PREVENTION. CADMIUM (CD) IS A HEAVY METAL AND A HIGHLY TOXIC POLLUTANT THAT IS RELEASED INTO THE ENVIRONMENT AS A BYPRODUCT OF MOST MODERN FACTORIES AND INDUSTRIES. CD ENTERS OUR BODY IN SIGNIFICANT QUANTITIES FROM CONTAMINATED WATER, CIGARETTE SMOKE, OR FOOD PRODUCT TO MANY DETRIMENTAL HEALTH HAZARDS. BASED ON CAUSAL ASSOCIATION ALL THE CD-RELATED OR DERIVED COMPOUNDS HAVE BEEN CLASSIFIED AS CARCINOGENS. IN THIS STUDY, WE PRESENT AN OVERVIEW OF THE PUBLISHED LITERATURE TO UNDERSTAND THE MOLECULAR MECHANISMS FOR CD-INDUCED CARCINOGENESIS AND ITS PREVENTION. IN ACUTE CD POISONING PRODUCTION OF REACTIVE OXYGEN SPECIES IS A KEY FACTOR. HOWEVER, CHRONIC CD EXPOSURE CAN TRANSFORM CELLS TO BECOME MORE RESISTANT TO OXIDATIVE STRESS. ALSO, AS AN EPIGENETIC MECHANISM CD ACTS INDIRECTLY ON DNA REPAIR MECHANISMS VIA ALTERATION OF REACTIONS UPSTREAM. THOSE TRANSFORMED CELLS ACQUIRE RESISTANCE TO APOPTOSIS AND DEREGULATION OF CALCIUM HOMEOSTASIS. LEADING TO UNCONTROLLED CARCINOGENIC CELL PROLIFERATION AND INHERENT DNA LESIONS. FLAVONOIDS COMMONLY FOUND IN PLANT FOODS HAVE BEEN SHOWN TO HAVE A PROTECTIVE EFFECT AGAINST CD-INDUCED CARCINOGENICITY. A WIDE VARIETY OF TUMORIGENIC MECHANISMS INVOLVED IN CHRONIC CD EXPOSURE AND THE BENEFICIAL EFFECTS OF FLAVONOIDS AGAINST CD-INDUCED CARCINOGENICITY NECESSITATE FURTHER INVESTIGATIONS. 2021 3 712 47 CADMIUM AND ITS EPIGENETIC EFFECTS. CADMIUM (CD) IS A TOXIC, NONESSENTIAL TRANSITION METAL AND CONTRIBUTES A HEALTH RISK TO HUMANS, INCLUDING VARIOUS CANCERS AND CARDIOVASCULAR DISEASES; HOWEVER, UNDERLYING MOLECULAR MECHANISMS REMAIN LARGELY UNKNOWN. CELLS TRANSMIT INFORMATION TO THE NEXT GENERATION VIA TWO DISTINCT WAYS: GENETIC AND EPIGENETIC. CHEMICAL MODIFICATIONS TO DNA OR HISTONE THAT ALTERS THE STRUCTURE OF CHROMATIN WITHOUT CHANGE OF DNA NUCLEOTIDE SEQUENCE ARE KNOWN AS EPIGENETICS. THESE HERITABLE EPIGENETIC CHANGES INCLUDE DNA METHYLATION, POST-TRANSLATIONAL MODIFICATIONS OF HISTONE TAILS (ACETYLATION, METHYLATION, PHOSPHORYLATION, ETC), AND HIGHER ORDER PACKAGING OF DNA AROUND NUCLEOSOMES. APART FROM DNA METHYLTRANSFERASES, HISTONE MODIFICATION ENZYMES SUCH AS HISTONE ACETYLTRANSFERASE, HISTONE DEACETYLASE, AND METHYLTRANSFERASE, AND MICRORNAS (MIRNAS) ALL INVOLVE IN THESE EPIGENETIC CHANGES. RECENT STUDIES INDICATE THAT CD IS ABLE TO INDUCE VARIOUS EPIGENETIC CHANGES IN PLANT AND MAMMALIAN CELLS IN VITRO AND IN VIVO. SINCE ABERRANT EPIGENETICS PLAYS A CRITICAL ROLE IN THE DEVELOPMENT OF VARIOUS CANCERS AND CHRONIC DISEASES, CD MAY CAUSE THE ABOVE-MENTIONED PATHOGENIC RISKS VIA EPIGENETIC MECHANISMS. HERE WE REVIEW THE IN VITRO AND IN VIVO EVIDENCE OF EPIGENETIC EFFECTS OF CD. THE AVAILABLE FINDINGS INDICATE THAT EPIGENETICS OCCURRED IN ASSOCIATION WITH CD INDUCTION OF MALIGNANT TRANSFORMATION OF CELLS AND PATHOLOGICAL PROLIFERATION OF TISSUES, SUGGESTING THAT EPIGENETIC EFFECTS MAY PLAY A ROLE IN CD TOXIC, PARTICULARLY CARCINOGENIC EFFECTS. THE FUTURE OF ENVIRONMENTAL EPIGENOMIC RESEARCH ON CD SHOULD INCLUDE THE ROLE OF EPIGENETICS IN DETERMINING LONG-TERM AND LATE-ONSET HEALTH EFFECTS FOLLOWING CD EXPOSURE. 2012 4 6370 37 THE ROLE OF MICRORNAS IN METAL CARCINOGEN-INDUCED CELL MALIGNANT TRANSFORMATION AND TUMORIGENESIS. MICRORNAS (MIRNAS), AN IMPORTANT COMPONENT OF EPIGENETIC MECHANISMS OF CARCINOGENESIS, HAVE BEEN SHOWN TO PLAY CRUCIAL ROLES IN CANCER INITIATION, METASTASIS, PROGNOSIS AND RESPONSES TO DRUG TREATMENT AND MAY SERVE AS BIOMARKERS FOR EARLY DIAGNOSIS OF CANCER AND TOOLS FOR CANCER THERAPY. METAL CARCINOGENS, SUCH AS ARSENIC, CADMIUM, HEXAVALENT CHROMIUM AND NICKEL, ARE WELL-ESTABLISHED HUMAN CARCINOGENS CAUSING VARIOUS CANCERS UPON LONG TERM EXPOSURE. HOWEVER, THE MECHANISM OF METAL CARCINOGENESIS HAS NOT BEEN WELL UNDERSTOOD, WHICH LIMITS OUR CAPABILITY TO EFFECTIVELY DIAGNOSE AND TREAT HUMAN CANCERS RESULTING FROM CHRONIC METAL CARCINOGEN EXPOSURE. OVER RECENT YEARS, THE ROLE OF MIRNAS IN METAL CARCINOGENESIS HAS BEEN ACTIVELY EXPLORED AND A GROWING BODY OF EVIDENCE INDICATES THE CRITICAL INVOLVEMENT OF MIRNAS IN METAL CARCINOGENESIS. THIS REVIEW AIMS TO DISCUSS RECENT STUDIES SHOWING THAT MIRNAS PLAY IMPORTANT ROLES IN METAL CARCINOGEN-INDUCED CELL MALIGNANT TRANSFORMATION AND TUMORIGENESIS. SOME THOUGHTS FOR FUTURE FURTHER STUDIES IN THIS FIELD ARE ALSO PRESENTED. 2016 5 4119 39 MECHANISMS OF CADMIUM CARCINOGENICITY IN THE GASTROINTESTINAL TRACT. CANCER, A SERIOUS PUBLIC HEALTH PROBLEM IN WORLDWIDE, RESULTS FROM AN EXCESSIVE AND UNCONTROLLED PROLIFERATION OF THE BODY CELLS WITHOUT OBVIOUS PHYSIOLOGICAL DEMANDS OF ORGANS. THE GASTROINTESTINAL TRACT, INCLUDING THE ESOPHAGUS, STOMACH AND INTESTINE, IS A UNIQUE ORGAN SYSTEM. IT HAS THE HIGHEST CANCER INCIDENCE AND CANCER- RELATED MORTALITY IN THE BODY AND IS INFLUENCEED BY BOTH GENETIC AND ENVIRONMENTAL FACTORS. AMONG THE VARIOUS CHEMICAL ELEMENTS RECOGNIZED IN THE NATURE, SOME OF THEM INCLUDING ZINC, IRON, COBALT, AND COPPER HAVE ESSENTIAL ROLES IN THE VARIOUS BIOCHEMICAL AND PHYSIOLOGICAL PROCESSES, BUT ONLY AT LOW LEVELS AND OTHERS SUCH AS CADMIUM, LEAD, MERCURY, ARSENIC, AND NICKEL ARE CONSIDERED AS THREATS FOR HUMAN HEALTH ESPECIALLY WITH CHRONIC EXPOSURE AT HIGH LEVELS. CADMIUM, AN ENVIRONMENT CONTAMINANT, CANNOT BE DESTROYED IN NATURE. THROUGH IMPAIRMENT OF VITAMIN D METABOLISM IN THE KIDNEY IT CAUSES NEPHROTOXICITY AND SUBSEQUENTLY BONE METABOLISM IMPAIRMENT AND FRAGILITY. THE MAJOR MECHANISMS INVOLVED IN CADMIUM CARCINOGENESIS COULD BE RELATED TO THE SUPPRESSION OF GENE EXPRESSION, INHIBITION OF DNA DAMAGE REPAIR, INHIBITION OF APOPTOSIS, AND INDUCTION OF OXIDATIVE STRESS. IN ADDITION, CADMIUM MAY ACT THROUGH ABERRANT DNA METHYLATION. CADMIUM AFFECTS MULTIPLE CELLULAR PROCESSES, INCLUDING SIGNAL TRANSDUCTION PATHWAYS, CELL PROLIFERATION, DIFFERENTIATION, AND APOPTOSIS. DOWN-REGULATION OF METHYLTRANSFERASES ENZYMES AND REDUCTION OF DNA METHYLATION HAVE BEEN STATED AS EPIGENETIC EFFECTS OF CADMIUM. FURTHERMORE, INCREASING INTRACELLULAR FREE CALCIUM ION LEVELS INDUCES NEURONAL APOPTOSIS IN ADDITION TO OTHER DELETERIOUS INFLUENCE ON THE STABILITY OF THE GENOME. 2015 6 5291 29 PROSTATE CARCINOGENESIS: INSIGHTS IN RELATION TO EPIGENETICS AND INFLAMMATION. PROSTATE CANCER IS A MULTIFACTORIAL DISEASE THAT MAINLY OCCURS DUE TO THE ACCUMULATION OF SOMATIC, GENETIC, AND EPIGENETIC CHANGES, RESULTING IN THE INACTIVATION OF TUMOR-SUPPRESSOR GENES AND ACTIVATION OF ONCOGENES. MUTATIONS IN GENES, SPECIFICALLY THOSE THAT CONTROL CELL GROWTH AND DIVISION OR THE REPAIR OF DAMAGED DNA, MAKE THE CELLS GROW AND DIVIDE UNCONTROLLABLY TO FORM A TUMOR. THE RISK OF DEVELOPING PROSTATE CANCER DEPENDS UPON THE GENE THAT HAS UNDERGONE THE MUTATION. IDENTIFYING SUCH GENETIC RISK FACTORS FOR PROSTATE CANCER POSES A CHALLENGE FOR THE RESEARCHERS. BESIDES GENETIC MUTATIONS, MANY EPIGENETIC ALTERATIONS, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS (METHYLATION, ACETYLATION, UBIQUITYLATION, SUMOYLATION, AND PHOSPHORYLATION) NUCLEOSOMAL REMODELING, AND CHROMOSOMAL LOOPING, HAVE SIGNIFICANTLY CONTRIBUTED TO THE ONSET OF PROSTATE CANCER AS WELL AS THE PROGNOSIS, DIAGNOSIS, AND TREATMENT OF PROSTATE CANCER. CHRONIC INFLAMMATION ALSO PLAYS A MAJOR ROLE IN THE ONSET AND PROGRESSION OF HUMAN CANCER, VIA MODIFICATIONS IN THE TUMOR MICROENVIRONMENT BY INITIATING EPITHELIALMESENCHYMAL TRANSITION AND REMODELING THE EXTRACELLULAR MATRIX. IN THIS ARTICLE, THE AUTHORS PRESENT A BRIEF HISTORY OF THE MECHANISMS AND POTENTIAL LINKS BETWEEN THE GENETIC ABERRATIONS, EPIGENETIC CHANGES, INFLAMMATION, AND INFLAMMASOMES THAT ARE KNOWN TO CONTRIBUTE TO THE PROGNOSIS OF PROSTATE CANCER. FURTHERMORE, THE AUTHORS EXAMINE AND DISCUSS THE CLINICAL POTENTIAL OF PROSTATE CARCINOGENESIS IN RELATION TO EPIGENETICS AND INFLAMMATION FOR ITS DIAGNOSIS AND TREATMENT.. 2021 7 480 37 ARSENIC-INDUCED CARCINOGENESIS: THE IMPACT OF MIRNA DYSREGULATION. ARSENIC IS A TOXIC METALLOID WIDELY PRESENT IN THE EARTH'S CRUST, AND IS A PROVEN HUMAN CARCINOGEN. CHRONIC ARSENIC EXPOSURE MAINLY THROUGH DRINKING WATER CAUSES SKIN, LUNG, AND URINARY BLADDER CANCERS, AND IS ASSOCIATED WITH LIVER, PROSTATE, AND KIDNEY CANCERS, CARDIOVASCULAR AND NEUROLOGICAL DISORDERS, AND DIABETES. SEVERAL MODES OF ACTION HAVE BEEN SUGGESTED IN ARSENIC CARCINOGENESIS. HOWEVER, THE MOLECULAR ETIOLOGY OF ARSENIC-INDUCED CANCER REMAINS UNCLEAR. RECENT EVIDENCE CLEARLY INDICATES THAT GENE EXPRESSION MODIFICATIONS INDUCED BY ARSENIC MAY INVOLVE EPIGENETIC ALTERATIONS, INCLUDING MIRNA DYSREGULATION. MANY MIRNAS HAVE BEEN IMPLICATED IN DIFFERENT HUMAN CANCERS AS A CONSEQUENCE OF LOSSES AND OR GAINS OF MIRNA FUNCTION THAT CONTRIBUTE TO CANCER DEVELOPMENT. PROGRESS IN IDENTIFYING MIRNA DYSREGULATION INDUCED BY ARSENIC HAS BEEN MADE USING DIFFERENT APPROACHES AND MODELS. THE PRESENT REVIEW DISCUSSES THE RECENT DATA REGARDING DYSREGULATED EXPRESSION OF MIRNA IN ARSENIC-INDUCED MALIGNANT TRANSFORMATION IN VITRO, GAPS IN CURRENT UNDERSTANDING AND DEFICIENCIES IN CURRENT MODELS FOR ARSENIC-INDUCED CARCINOGENESIS, AND FUTURE DIRECTIONS OF RESEARCH THAT WOULD IMPROVE OUR KNOWLEDGE REGARDING THE MECHANISMS INVOLVED IN ARSENIC-INDUCED CARCINOGENESIS. 2018 8 6809 29 [EPIGENETICS IN INFLAMMATORY SYSTEMIC DISEASES]. IN ADDITION TO ANALYSIS OF THE GENETIC CODE, IN RECENT YEARS MORE AND MORE STUDIES HAVE CONCENTRATED ON CHANGES IN THE EPIGENETIC CODE. EPIGENETIC MECHANISMS DETERMINE WHICH GENES IN A CELL ARE TRANSCRIBED AND THUS FORM THE PHENOTYPE OF A CELL. THE EPIGENETIC CODE CAN BE CHANGED BY ENVIRONMENTAL INFLUENCES, WHICH ALLOWS CELLS TO ADAPT TO LONGSTANDING CHANGES IN THE ENVIRONMENT. THEREFORE, IT IS FEASIBLE TO ASSUME THAT EPIGENETIC CHANGES ARE THE MOLECULAR BASIS FOR LONG-TERM EFFECTS OF THE ENVIRONMENT ON DISEASE DEVELOPMENT. IN PARTICULAR IN TUMORS AND CHRONIC INFLAMMATORY DISEASES EPIGENETIC CHANGES WERE FOUND TO CORRELATE WITH DISEASE SEVERITY AND PROGRESSION. KNOWLEDGE ABOUT THESE EPIGENETIC CHANGES MIGHT HELP THAT EPIGENETIC MODIFICATIONS CAN BE USED IN THE FUTURE AS BIOMARKERS, PROGNOSTIC FACTORS AND THERAPEUTIC TARGETS. 2014 9 928 25 CHRONIC INFLAMMATION, THE TUMOR MICROENVIRONMENT AND CARCINOGENESIS. CHRONIC INFLAMMATION OFTEN PRECEDES OR ACCOMPANIES A SUBSTANTIAL NUMBER OF CANCERS. INDEED, ANTI-INFLAMMATORY THERAPIES HAVE SHOWN EFFICACY IN CANCER PREVENTION AND TREATMENT. THE EXACT MECHANISMS THAT TURN A WOUND HEALING PROCESS INTO A CANCER PRECURSOR ARE TOPICS OF INTENSE RESEARCH. A PATHOGENIC LINK HAS BEEN IDENTIFIED BETWEEN INFLAMMATORY MEDIATORS, INFLAMMATION RELATED GENE POLYMORPHISMS AND CARCINOGENESIS. ANIMAL MODELS OF CANCER HAVE BEEN INSTRUMENTAL IN DEMONSTRATING THE DIVERSITY OF MECHANISMS THROUGH WHICH EVERY TUMOR COMPARTMENT AND TUMOR STAGE MAY BE AFFECTED BY THE UNDERLYING INFLAMMATORY PROCESS. IN THIS REVIEW, WE FOCUS ON THE INTERACTION BETWEEN CHRONIC INFLAMMATION, TUMOR STEM CELLS AND THE TUMOR MICROENVIRONMENT. WE SUMMARIZE THE PROPOSED MECHANISMS THAT LEAD TO THE RECRUITMENT OF BONE MARROW DERIVED CELLS AND EXPLORE THE GENETIC AND EPIGENETIC ALTERATIONS THAT MAY OCCUR IN INFLAMMATION ASSOCIATED CANCERS. 2009 10 860 35 CHROMATIN MODIFICATIONS DURING REPAIR OF ENVIRONMENTAL EXPOSURE-INDUCED DNA DAMAGE: A POTENTIAL MECHANISM FOR STABLE EPIGENETIC ALTERATIONS. EXPOSURES TO ENVIRONMENTAL TOXICANTS AND TOXINS CAUSE EPIGENETIC CHANGES THAT LIKELY PLAY A ROLE IN THE DEVELOPMENT OF DISEASES ASSOCIATED WITH EXPOSURE. THE MECHANISM BEHIND THESE EXPOSURE-INDUCED EPIGENETIC CHANGES IS CURRENTLY UNKNOWN. ONE COMMONALITY BETWEEN MOST ENVIRONMENTAL EXPOSURES IS THAT THEY CAUSE DNA DAMAGE EITHER DIRECTLY OR THROUGH CAUSING AN INCREASE IN REACTIVE OXYGEN SPECIES, WHICH CAN DAMAGE DNA. LIKE TRANSCRIPTION, DNA DAMAGE REPAIR MUST OCCUR IN THE CONTEXT OF CHROMATIN REQUIRING BOTH HISTONE MODIFICATIONS AND ATP-DEPENDENT CHROMATIN REMODELING. THESE CHROMATIN CHANGES AID IN DNA DAMAGE ACCESSIBILITY AND SIGNALING. SEVERAL PROTEINS AND COMPLEXES INVOLVED IN EPIGENETIC SILENCING DURING BOTH DEVELOPMENT AND CANCER HAVE BEEN FOUND TO BE LOCALIZED TO SITES OF DNA DAMAGE. THE CHROMATIN-BASED RESPONSE TO DNA DAMAGE IS CONSIDERED A TRANSIENT EVENT, WITH CHROMATIN BEING RESTORED TO NORMAL AS DNA DAMAGE REPAIR IS COMPLETED. HOWEVER, IN INDIVIDUALS CHRONICALLY EXPOSED TO ENVIRONMENTAL TOXICANTS OR WITH CHRONIC INFLAMMATORY DISEASE, REPEATED DNA DAMAGE-INDUCED CHROMATIN REARRANGEMENT MAY ULTIMATELY LEAD TO PERMANENT EPIGENETIC ALTERATIONS. UNDERSTANDING THE MECHANISM BEHIND EXPOSURE-INDUCED EPIGENETIC CHANGES WILL ALLOW US TO DEVELOP STRATEGIES TO PREVENT OR REVERSE THESE CHANGES. THIS REVIEW FOCUSES ON EPIGENETIC CHANGES AND DNA DAMAGE INDUCED BY ENVIRONMENTAL EXPOSURES, THE CHROMATIN CHANGES THAT OCCUR AROUND SITES OF DNA DAMAGE, AND HOW THESE TRANSIENT CHROMATIN CHANGES MAY LEAD TO HERITABLE EPIGENETIC ALTERATIONS AT SITES OF CHRONIC EXPOSURE. 2014 11 1912 34 ENVIRONMENT, DIET AND CPG ISLAND METHYLATION: EPIGENETIC SIGNALS IN GASTROINTESTINAL NEOPLASIA. THE EPITHELIAL SURFACES OF THE MAMMALIAN ALIMENTARY TRACT ARE CHARACTERISED BY VERY HIGH RATES OF CELL PROLIFERATION AND DNA SYNTHESIS, AND IN HUMANS THEY ARE HIGHLY SUSCEPTIBLE TO CANCER. THE ROLE OF SOMATIC MUTATIONS AS DRIVERS OF CARCINOGENESIS IN THE ALIMENTARY TRACT IS WELL ESTABLISHED, BUT THE IMPORTANCE OF GENE SILENCING BY EPIGENETIC MECHANISMS IS INCREASINGLY RECOGNISED. METHYLATION OF CPG ISLANDS IS AN IMPORTANT COMPONENT OF THE EPIGENETIC CODE THAT REGULATES GENE EXPRESSION DURING DEVELOPMENT AND NORMAL CELLULAR DIFFERENTIATION, AND A NUMBER OF GENES ARE WELL KNOWN TO BECOME ABNORMALLY METHYLATED DURING THE DEVELOPMENT OF TUMOURS OF THE OESOPHAGUS, STOMACH AND COLORECTUM. ABERRANT PATTERNS OF DNA METHYLATION DEVELOP AS A RESULT OF PATHOLOGICAL PROCESSES SUCH AS CHRONIC INFLAMMATION, AND IN RESPONSE TO VARIOUS DIETARY FACTORS, INCLUDING IMBALANCES IN THE SUPPLY OF METHYL DONORS, PARTICULARLY FOLATES, AND EXPOSURE TO DNA METHYLTRANSFERASE INHIBITORS, WHICH INCLUDE POLYPHENOLS AND POSSIBLY ISOTHIOCYANATES FROM PLANT FOODS. HOWEVER THE IMPORTANCE OF THESE ENVIRONMENTAL INTERACTIONS IN HUMAN HEALTH AND DISEASE REMAINS TO BE ESTABLISHED. RECENT MOVES TO MODIFY THE EXPOSURE OF HUMAN POPULATIONS TO FOLATE, BY MANDATORY SUPPLEMENTATION OF CEREAL FOODS, EMPHASISE THE IMPORTANCE OF UNDERSTANDING THE SUSCEPTIBILITY OF THE HUMAN EPIGENOME TO DIETARY AND OTHER ENVIRONMENTAL EFFECTS. 2008 12 1405 31 DIETARY FACTORS AND EPIGENETIC REGULATION FOR PROSTATE CANCER PREVENTION. THE ROLE OF EPIGENETIC ALTERATIONS IN VARIOUS HUMAN CHRONIC DISEASES HAS GAINED INCREASING ATTENTION AND HAS RESULTED IN A PARADIGM SHIFT IN OUR UNDERSTANDING OF DISEASE SUSCEPTIBILITY. IN THE FIELD OF CANCER RESEARCH, E.G., GENETIC ABNORMALITIES/MUTATIONS HISTORICALLY WERE VIEWED AS PRIMARY UNDERLYING CAUSES; HOWEVER, EPIGENETIC MECHANISMS THAT ALTER GENE EXPRESSION WITHOUT AFFECTING DNA SEQUENCE ARE NOW RECOGNIZED AS BEING OF EQUAL OR GREATER IMPORTANCE FOR ONCOGENESIS. METHYLATION OF DNA, MODIFICATION OF HISTONES, AND INTERFERING MICRORNA (MIRNA) COLLECTIVELY REPRESENT A CADRE OF EPIGENETIC ELEMENTS DYSREGULATED IN CANCER. TARGETING THE EPIGENOME WITH COMPOUNDS THAT MODULATE DNA METHYLATION, HISTONE MARKS, AND MIRNA PROFILES REPRESENTS AN EVOLVING STRATEGY FOR CANCER CHEMOPREVENTION, AND THESE APPROACHES ARE STARTING TO SHOW PROMISE IN HUMAN CLINICAL TRIALS. ESSENTIAL MICRONUTRIENTS SUCH AS FOLATE, VITAMIN B-12, SELENIUM, AND ZINC AS WELL AS THE DIETARY PHYTOCHEMICALS SULFORAPHANE, TEA POLYPHENOLS, CURCUMIN, AND ALLYL SULFUR COMPOUNDS ARE AMONG A GROWING LIST OF AGENTS THAT AFFECT EPIGENETIC EVENTS AS NOVEL MECHANISMS OF CHEMOPREVENTION. TO ILLUSTRATE THESE CONCEPTS, THE CURRENT REVIEW HIGHLIGHTS THE INTERACTIONS AMONG NUTRIENTS, EPIGENETICS, AND PROSTATE CANCER SUSCEPTIBILITY. IN PARTICULAR, WE FOCUS ON EPIGENETIC DYSREGULATION AND THE IMPACT OF SPECIFIC NUTRIENTS AND FOOD COMPONENTS ON DNA METHYLATION AND HISTONE MODIFICATIONS THAT CAN ALTER GENE EXPRESSION AND INFLUENCE PROSTATE CANCER PROGRESSION. 2011 13 2704 29 EXERCISE AND COLORECTAL CANCER: PREVENTION AND MOLECULAR MECHANISMS. EXERCISE AND PHYSICAL ACTIVITY HAVE BEEN SHOWN TO BE STRONGLY ASSOCIATED WITH A DECREASED INCIDENCE RATE OF VARIOUS CHRONIC DISEASES ESPECIALLY NUMEROUS HUMAN MALIGNANCIES. A HUGE NUMBER OF CLINICAL TRIALS AND META-ANALYSIS HAVE DEMONSTRATED THAT EXERCISE IS SIGNIFICANTLY EFFECTIVE IN LOWERING THE RISK OF COLORECTAL CANCER. IN ADDITION, IT IS SUGGESTED AS AN EFFECTIVE THERAPEUTIC MODALITY AGAINST THIS CANCER TYPE. THEREFORE, IN THIS REVIEW, WE WILL REVIEW COMPREHENSIBLY THE EFFECTS OF EXERCISE IN PREVENTING, TREATING, AND ALLEVIATING THE ADVERSE EFFECTS OF CONVENTIONAL THERAPEUTIC OPTIONS IN COLORECTAL CANCER. MOREOVER, THE POSSIBLE MECHANISMS UNDERLYING THE POSITIVE EFFECTS OF EXERCISE AND PHYSICAL ACTIVITY IN COLORECTAL CANCER, INCLUDING REGULATION OF INFLAMMATION, APOPTOSIS, GROWTH FACTOR AXIS, IMMUNITY, EPIGENETIC, ETC. WILL BE ALSO DISCUSSED. 2022 14 2282 35 EPIGENETIC REGULATION IN EXPOSOME-INDUCED TUMORIGENESIS: EMERGING ROLES OF NCRNAS. ENVIRONMENTAL FACTORS, INCLUDING POLLUTANTS AND LIFESTYLE, CONSTITUTE A SIGNIFICANT ROLE IN SEVERE, CHRONIC PATHOLOGIES WITH AN ESSENTIAL SOCIETAL, ECONOMIC BURDEN. THE MEASUREMENT OF ALL ENVIRONMENTAL EXPOSURES AND ASSESSING THEIR CORRELATION WITH EFFECTS ON INDIVIDUAL HEALTH IS DEFINED AS THE EXPOSOME, WHICH INTERACTS WITH OUR UNIQUE CHARACTERISTICS SUCH AS GENETICS, PHYSIOLOGY, AND EPIGENETICS. EPIGENETICS INVESTIGATES MODIFICATIONS IN THE EXPRESSION OF GENES THAT DO NOT DEPEND ON THE UNDERLYING DNA SEQUENCE. SOME STUDIES HAVE CONFIRMED THAT ENVIRONMENTAL FACTORS MAY PROMOTE DISEASE IN INDIVIDUALS OR SUBSEQUENT PROGENY THROUGH EPIGENETIC ALTERATIONS. VARIATIONS IN THE EPIGENETIC MACHINERY CAUSE A SPECTRUM OF DIFFERENT DISORDERS SINCE THESE MECHANISMS ARE MORE SENSITIVE TO THE ENVIRONMENT THAN THE GENOME, DUE TO THE INHERENT REVERSIBLE NATURE OF THE EPIGENETIC LANDSCAPE. SEVERAL EPIGENETIC MECHANISMS, INCLUDING MODIFICATIONS IN DNA (E.G., METHYLATION), HISTONES, AND NONCODING RNAS CAN CHANGE GENOME EXPRESSION UNDER THE EXOGENOUS INFLUENCE. NOTABLY, THE ROLE OF LONG NONCODING RNAS IN EPIGENETIC PROCESSES HAS NOT BEEN WELL EXPLORED IN THE CONTEXT OF EXPOSOME-INDUCED TUMORIGENESIS. IN THE PRESENT REVIEW, OUR SCOPE IS TO PROVIDE RELEVANT EVIDENCE INDICATING THAT EPIGENETIC ALTERATIONS MEDIATE THOSE DETRIMENTAL EFFECTS CAUSED BY EXPOSURE TO ENVIRONMENTAL TOXICANTS, FOCUSING MAINLY ON A MULTI-STEP REGULATION BY DIVERSE NONCODING RNAS SUBTYPES. 2022 15 1844 33 EFFECTS OF THE LIFESTYLE HABITS IN BREAST CANCER TRANSCRIPTIONAL REGULATION. THROUGH RESEARCH CARRIED OUT IN THE LAST 25 YEARS ABOUT THE BREAST CANCER ETIOLOGY, IT HAS BEEN POSSIBLE TO ESTIMATE THAT LESS THAN 10 % OF PATIENTS WHO ARE DIAGNOSED WITH THE CONDITION ARE CARRIERS OF SOME GERMLINE OR SOMATIC MUTATION. THE CLINICAL REPORTS OF BREAST CANCER PATIENTS WITH HEALTHY TWINS AND THE DEVELOPMENT OF DISEASE IN WOMEN WITHOUT HIGH PENETRANCE MUTATIONS DETECTED, WARN THE PARTICIPATION MORE FACTORS IN THE TRANSFORMATION PROCESS. THE HIGH INCIDENCE OF MAMMARY ADENOCARCINOMA IN THE MODERN WOMAN AND THE URGENT NEED FOR NEW METHODS OF PREVENTION AND EARLY DETECTION HAVE DEMANDED MORE INFORMATION ABOUT THE ROLE THAT ENVIRONMENT AND LIFESTYLE HAVE ON THE TRANSFORMATION OF MAMMARY GLAND EPITHELIAL CELLS. OBESITY, ALCOHOLISM AND SMOKING ARE FACTORS THAT HAVE SHOWN A CLOSE CORRELATION WITH THE RISK OF DEVELOPING BREAST CANCER. AND ALTHOUGH THESE CONDITIONS AFFECT DIFFERENT CELL REGULATION LEVELS, THE STUDY OF ITS EFFECTS IN THE MECHANISMS OF TRANSCRIPTIONAL AND EPIGENETIC REGULATION IS CONSIDERED CRITICAL FOR A BETTER UNDERSTANDING OF THE LOSS OF IDENTITY OF EPITHELIAL CELLS DURING CARCINOGENESIS OF THIS TISSUE. THE MAIN OBJECTIVE OF THIS REVIEW WAS TO ESTABLISH THE IMPORTANCE OF CHANGES OCCURRING TO TRANSCRIPTIONAL LEVEL IN THE MAMMARY GLAND AS A CONSEQUENCE OF ACUTE OR CHRONIC EXPOSURE TO HARMFUL PRODUCTS SUCH AS OBESITY-CAUSING FOODS, ETHANOL AND CIGARETTE SMOKE COMPONENTS. AT ANALYZE THE MAIN STUDIES RELATED TO TOPIC, IT HAS CONCLUDED THAT THE UNDERSTANDING OF EFFECTS CAUSED BY THE LIFESTYLE FACTORS IN PERFORMANCE OF THE TRANSCRIPTIONAL MECHANISMS THAT DETERMINE GENE EXPRESSION OF THE MAMMARY GLAND EPITHELIAL CELLS, MAY HELP EXPLAIN THE DEVELOPMENT OF THIS DISEASE IN WOMEN WITHOUT GENETIC PROPENSITY AND DIFFERENT PHENOTYPIC MANIFESTATIONS OF THIS CANCER TYPE. 2016 16 4840 33 ONCOGENOMIC DISRUPTIONS IN ARSENIC-INDUCED CARCINOGENESIS. CHRONIC EXPOSURE TO ARSENIC AFFECTS MORE THAN 200 MILLION PEOPLE WORLDWIDE, AND HAS BEEN ASSOCIATED WITH MANY ADVERSE HEALTH EFFECTS, INCLUDING CANCER IN SEVERAL ORGANS. THERE IS ACCUMULATING EVIDENCE THAT ARSENIC BIOTRANSFORMATION, A STEP IN THE ELIMINATION OF ARSENIC FROM THE HUMAN BODY, CAN INDUCE CHANGES AT A GENETIC AND EPIGENETIC LEVEL, LEADING TO CARCINOGENESIS. AT THE GENETIC LEVEL, ARSENIC INTERFERES WITH KEY CELLULAR PROCESSES SUCH AS DNA DAMAGE-REPAIR AND CHROMOSOMAL STRUCTURE, LEADING TO GENOMIC INSTABILITY. AT THE EPIGENETIC LEVEL, ARSENIC PLACES A HIGH DEMAND ON THE CELLULAR METHYL POOL, LEADING TO GLOBAL HYPOMETHYLATION AND HYPERMETHYLATION OF SPECIFIC GENE PROMOTERS. THESE ARSENIC-ASSOCIATED DNA ALTERATIONS RESULT IN THE DEREGULATION OF BOTH ONCOGENIC AND TUMOUR-SUPPRESSIVE GENES. FURTHERMORE, RECENT REPORTS HAVE IMPLICATED ABERRANT EXPRESSION OF NON-CODING RNAS AND THE CONSEQUENTIAL DISRUPTION OF SIGNALING PATHWAYS IN THE CONTEXT OF ARSENIC-INDUCED CARCINOGENESIS. THIS ARTICLE PROVIDES AN OVERVIEW OF THE ONCOGENOMIC ANOMALIES ASSOCIATED WITH ARSENIC EXPOSURE AND CONVEYS THE IMPORTANCE OF NON-CODING RNAS IN THE ARSENIC-INDUCED CARCINOGENIC PROCESS. 2017 17 6213 29 THE INTESTINAL EPITHELIAL CELL CYCLE: UNCOVERING ITS 'CRYPTIC' NATURE. PURPOSE OF REVIEW: TO DISCUSS THE RECENT LANDMARK FINDINGS THAT HAVE INCREASED OUR UNDERSTANDING NOT ONLY OF THE ROLE OF THE EPITHELIAL CELL CYCLE IN THE HOMEOSTASIS OF THE SMALL INTESTINE, BUT ALSO ITS RELEVANCE TO INFLAMMATION AND CANCER. RECENT FINDINGS: RECENT DATA HAVE UNVEILED NOVEL INFORMATION ON PROTEIN INTERACTIONS DIRECTLY INVOLVED IN THE CELL CYCLE AS WELL AS IN THE PATHWAYS THAT TRANSDUCE EXTERNAL ENVIRONMENTAL SIGNALS TO THE CELL CYCLE. A GROWING BODY OF THE RECENT EVIDENCE CONFIRMS THE IMPORTANCE OF FOOD AS WELL AS HORMONAL REGULATION IN THE GUT ON CELL CYCLE. INFORMATION ON THE CONTRIBUTION OF THE EPITHELIAL MICROENVIRONMENT, INCLUDING THE MICROBIOTA, HAS GROWN SUBSTANTIALLY IN THE RECENT YEARS AS WELL AS ON THE GENE-ENVIRONMENT INTERACTIONS AND THE MULTIPLE EPIGENETIC MECHANISMS INVOLVED IN REGULATING CELL-CYCLE PROTEINS AND SIGNALLING. FINALLY, FURTHER STUDIES INVESTIGATING THE DYSREGULATION OF THE CELL CYCLE DURING INFLAMMATION AND PROLIFERATION HAVE INCREASED OUR UNDERSTANDING OF THE PATHOPHYSIOLOGY OF CHRONIC INFLAMMATORY DISEASES AND CANCER. SUMMARY: THIS REVIEW HIGHLIGHTS SOME OF THE MOST RECENT ADVANCES THAT FURTHER EMPHASIZE THE IMPORTANCE OF THE CELL CYCLE IN THE SMALL INTESTINE DURING HOMEOSTASIS AS WELL AS IN INFLAMMATION AND CANCER. 2015 18 6771 30 [ACQUIRED DISORDERS AND EPIGENETICS]. EPIGENETIC MODIFICATIONS, INVOLVING DNA METHYLATION AND HISTONE MODIFICATIONS, ARE MAINTAINED UPON SOMATIC CELL REPLICATION, AND ARE FUNDAMENTAL MECHANISMS FOR CELLULAR MEMORY. DNA METHYLATION OF PROMOTER CPG ISLANDS OF TUMOR-SUPPRESSOR GENES CAN SILENCE THEIR DOWNSTREAM GENES, AND CAN BE CAUSALLY INVOLVED IN CANCER DEVELOPMENT AND PROGRESSION. SINCE THIS EFFECT IS THE SAME WITH THAT OF INACTIVATING MUTATIONS, THE NATURES OF DNA METHYLATION WERE ONCE CONSIDERED TO BE SIMILAR TO MUTATIONS. HOWEVER, RECENTLY, IT WAS REVEALED THAT A LARGE NUMBER OF EPIGENETIC ALTERATIONS ARE PRESENT IN A SINGLE CANCER CELL, THAT A LARGE NUMBER OF CELLS HAVE AN EPIGENETIC ALTERATION OF A SPECIFIC GENE IN NON-CANCEROUS, THUS POLYCLONAL, TISSUES, THAT GENE SPECIFICITY IN METHYLATION INDUCTION IS PRESENT ACCORDING TO TISSUE TYPES AND INDUCERS, AND THAT CHRONIC INFLAMMATION IS DEEPLY INVOLVED IN METHYLATION INDUCTION. THESE FACTS SUGGEST THAT EPIGENETIC ALTERATIONS OF KEY GENES INVOLVED IN ACQUIRED CHRONIC DISORDERS CAN BE PRESENT IN A SIGNIFICANT FRACTION OF CELLS IN A TISSUE, AND THUS CAN IMPAIR THE FUNCTION OF THE TISSUE. ASSOCIATIONS BETWEEN EPIGENETIC ALTERATIONS AND BEHAVIOR, MEMORY, MENTAL DISORDERS, NEUROLOGICAL DISORDERS, METABOLIC DISORDERS, ALLERGY, AUTOIMMUNE DISORDERS, AND OTHER DISORDERS HAVE BEEN REPORTED. FURTHER RESEARCH IN THE FIELD IS NECESSARY TO CLARIFY THE CAUSAL ROLES OF THESE EPIGENETIC ALTERATIONS IN DISEASE DEVELOPMENT, AND TO APPLY THE FINDINGS TO NEW STRATEGIES OF DISEASE PREVENTION, DIAGNOSIS, AND TREATMENT. 2010 19 6715 32 VITAMIN A AND THE EPIGENOME. THE EPIGENETIC PHENOMENA REFER TO HERITABLE CHANGES IN GENE EXPRESSION OTHER THAN THOSE IN THE DNA SEQUENCE, SUCH AS DNA METHYLATION AND HISTONE MODIFICATIONS. MAJOR RESEARCH PROGRESS IN THE LAST FEW YEARS HAS PROVIDED FURTHER PROOF THAT ENVIRONMENTAL FACTORS, INCLUDING DIET AND NUTRITION, CAN INFLUENCE PHYSIOLOGIC AND PATHOLOGIC PROCESSES THROUGH EPIGENETIC ALTERATIONS, WHICH IN TURN INFLUENCE GENE EXPRESSION. THIS INFLUENCE IS TERMED NUTRITIONAL EPIGENETICS, AND ONE PROMINENT EXAMPLE IS THE REGULATION OF GENE TRANSCRIPTION BY VITAMIN A THROUGH INTERACTION TO ITS NUCLEAR RECEPTOR. VITAMIN A IS CRITICAL THROUGHOUT LIFE. TOGETHER WITH ITS DERIVATIVES, IT REGULATES DIVERSE PROCESSES INCLUDING REPRODUCTION, EMBRYOGENESIS, VISION, GROWTH, CELLULAR DIFFERENTIATION AND PROLIFERATION, MAINTENANCE OF EPITHELIAL CELLULAR INTEGRITY AND IMMUNE FUNCTION. HERE WE REVIEW THE EPIGENETIC ROLE OF VITAMIN A IN CANCER, STEM CELLS DIFFERENTIATION, PROLIFERATION, AND IMMUNITY. THE DATA PRESENTED HERE SHOW THAT RETINOIC ACID IS A POTENT AGENT CAPABLE OF INDUCING ALTERATIONS IN EPIGENETIC MODIFICATIONS THAT PRODUCE VARIOUS EFFECTS ON THE PHENOTYPE. MEDICAL BENEFITS OF VITAMIN A AS AN EPIGENETIC MODULATOR, ESPECIALLY WITH RESPECT TO ITS CHRONIC USE AS NUTRITIONAL SUPPLEMENT, SHOULD RELY ON OUR FURTHER UNDERSTANDING OF ITS EPIGENETIC EFFECTS DURING HEALTH AND DISEASE, AS WELL AS THROUGH DIFFERENT GENERATIONS. 2017 20 45 25 A COMPREHENSIVE REVIEW ON RNA INTERFERENCE-MEDIATED TARGETING OF INTERLEUKINS AND ITS POTENTIAL THERAPEUTIC IMPLICATIONS IN COLON CANCER. COLON CANCER IS THE WORLD'S FOURTH LEADING CAUSE OF DEATH. IT IS CANCER OF THE LATTER PART OF THE LARGE INTESTINE, I.E. THE COLON. CHRONIC INFLAMMATION OVER A LONG PERIOD ALSO LEADS TO THE DEVELOPMENT OF CANCER. CANCER IN THE COLON REGION IS ARDUOUS TO DIAGNOSE AND IS DETECTED AT A LATER STAGE WHEN IT METASTASIZES TO OTHER PARTS OF THE BODY LIKE THE LIVER, LUNGS, PERITONEUM, ETC. COLON CANCER IS A GREAT EXAMPLE OF SOLID TUMOURS ASSOCIATED WITH CHRONIC INFLAMMATION. ALTHOUGH CONVENTIONAL THERAPIES ARE EFFECTIVE, THEY LOSE THEIR EFFECTIVENESS BEYOND A CERTAIN POINT. RELAPSE OF THE DISEASE OCCURS FREQUENTLY. RNA INTERFERENCE (RNAI) IS EMERGING AS A GREAT TOOL TO SPECIFICALLY ATTACK THE CANCER CELLS OF A TARGET SITE LIKE THE COLON. RNAI DEALS WITH EPIGENETIC CHANGES MADE IN THE DEFECTIVE CELLS WHICH ULTIMATELY LEADS TO THEIR DEATH WITHOUT HARMING THE HEALTHY CELLS. IN THIS REVIEW, TWO TYPES OF EPIGENETIC MODULATORS HAVE BEEN CONSIDERED, NAMELY SIRNA AND MIRNA, AND THEIR EFFECT ON INTERLEUKINS. INTERLEUKINS, A CLASS OF CYTOKINES, ARE MAJOR INFLAMMATORY RESPONSES OF THE BODY THAT ARE RELEASED BY IMMUNE CELLS LIKE LEUKOCYTES AND MACROPHAGES. SOME OF THESE INTERLEUKINS ARE PRO-INFLAMMATORY, THEREBY PROMOTING INFLAMMATION WHICH EVENTUALLY CAUSES CANCER. RNAI CAN PREVENT COLON CANCER BY INHIBITING PRO-INFLAMMATORY INTERLEUKINS. 2023