1 4529 120 MULTIGENERATIONAL GRAPHENE OXIDE INTOXICATION RESULTS IN REPRODUCTION DISORDERS AT THE MOLECULAR LEVEL OF VITELLOGENIN PROTEIN EXPRESSION IN ACHETA DOMESTICUS. THE ANTHROPOGENIC ACTIVITIES MAY LEAD TO ACCUMULATION OF GRAPHENE OXIDE (GO) POLLUTION IN THE ENVIRONMENT. ORGANISMS EXPOSED TO CHRONIC OR MULTIGENERATIONAL GO INTOXICATION CAN PRESENT REPRODUCTION DEPLETION. VITELLOGENIN (VG) HAS BEEN USED AS A PARAMETER FOR EVALUATING FEMALE FERTILITY DUE TO ITS IMPORTANCE IN EMBRYO NUTRITION. IN THIS STUDY, WE USED A PROMISING MODEL ORGANISM, ACHETA DOMESTICUS, WHICH WAS INTOXICATED WITH GO IN FOOD FOR THREE GENERATIONS. THE AIM OF THE STUDY WAS TO INVESTIGATE THE PROCESS OF VG SYNTHESIS IN CRICKETS DEPENDING ON THE EXPOSURE TIME, GO CONCENTRATION, AND AGE OF THE FEMALES. THE RESULTS REVEALED THAT CHRONIC GO INTOXICATION HAD ADVERSE EFFECTS ON THE VG EXPRESSION PATTERN. THE 1ST GENERATION OF INSECTS SHOWING LOW VG EXPRESSION WAS MOST AFFECTED. THE 2ND GENERATION OF A. DOMESTICUS PRESENTED A HIGH VG EXPRESSION. THE LAST INVESTIGATED GENERATION SEEMED TO COPE WITH STRESS CAUSED BY GO, AND THE VG EXPRESSION WAS BALANCED. WE SUGGEST THAT THE EPIGENETIC MECHANISMS MAY PLAY A ROLE IN THE INFORMATION TRANSFER TO THE NEXT GENERATIONS ON HOW TO REACT TO THE RISK FACTOR AND KEEP REPRODUCTION AT A HIGH RATE. WE SUSPECT THAT CHRONIC GO INTOXICATION CAN DISTURB THE REGULAR FORMATION OF THE VG QUATERNARY STRUCTURE, RESULTING IN CONSEQUENCES FOR DEVELOPING AN EMBRYO. 2021 2 3485 28 IDENTIFICATION OF CIRCULAR RNAS EXPRESSION PATTERN IN CAPRINE FETAL FIBROBLAST CELLS EXPOSED TO A CHRONIC NON-CYTOTOXIC DOSE OF GRAPHENE OXIDE-SILVER NANOPARTICLE NANOCOMPOSITES. THE WIDESPREAD USE OF GRAPHENE OXIDE-SILVER NANOPARTICLE NANOCOMPOSITES (GO-AGNPS) IN BIOMEDICAL SCIENCES IS INCREASING THE CHANCES OF HUMAN AND ANIMAL EXPOSURE TO ITS CHRONIC NON-TOXIC DOSES. EXPOSURE TO AGNPS-RELATED NANOMATERIALS MAY RESULT IN THE NEGATIVE EFFECT ON THE DAM, FETUS AND OFFSPRING. HOWEVER, THERE ARE ONLY LITTLE AVAILABLE INFORMATION FOR PROFOUND UNDERSTANDING OF THE EPIGENETIC ALTERATION IN THE CELLS AND ANIMALS CAUSED BY LOW-DOSE CHRONIC EXPOSURE OF GO-AGNPS. THE PRESENT STUDY INVESTIGATED THE EFFECT OF 0.5 MUG/ML GO-AGNPS FOR 10 WEEKS ON THE DIFFERENTIAL EXPRESSION OF CIRCULAR RNAS (CIRCRNAS) IN CAPRINE FETAL FIBROBLAST CELLS (CFFCS), AND THIS DOSE OF GO-AGNPS DID NOT AFFECT CELL VIABILITY AND ROS LEVEL. WE PREDICTED THE FUNCTIONS OF THOSE DIFFERENTIALLY EXPRESSED (DE) CIRCRNAS IN CFFCS BY BIOINFORMATICS ANALYSIS. FURTHERMORE, WE VALIDATED THE EXPRESSION OF TEN DE CIRCRNAS USING QUANTITATIVE REAL-TIME REVERSE TRANSCRIPTION-POLYMERASE CHAIN REACTION (QRT-PCR) TO ENSURE THE RELIABILITY OF THE SEQUENCING DATA. OUR RESULTS SHOWED THAT THE DE CIRCRNAS MAY POTENTIALLY REGULATE THE GO-AGNPS-INDUCING EPIGENETIC TOXICITY THROUGH A REGULATORY NETWORK CONSISTED OF CIRCRNAS, MIRNAS AND MESSENGER RNAS (MRNAS). THEREFORE, THE EPIGENETICS TOXICITY IS ESSENTIAL TO ASSESS THE BIOSAFETY LEVEL OF GO-AGNPS. 2023 3 4312 29 MICRORNAS AS A SUITABLE BIOMARKER TO DETECT THE EFFECTS OF LONG-TERM EXPOSURES TO NANOMATERIALS. STUDIES ON TIO(2)NP AND MWCNT. THE PRESENCE OF NANOMATERIALS (NMS) IN THE ENVIRONMENT MAY REPRESENT A SERIOUS RISK TO HUMAN HEALTH, ESPECIALLY IN A SCENARIO OF CHRONIC EXPOSURE. TO EVALUATE THE POTENTIAL RELATIONSHIP BETWEEN NM-INDUCED EPIGENETIC ALTERATIONS AND CARCINOGENESIS, THE PRESENT STUDY ANALYZED A PANEL OF 33 MIRNAS RELATED TO THE CELL TRANSFORMATION PROCESS IN BEAS-2B CELLS TRANSFORMED BY TIO(2)NP AND LONG-TERM MWCNT EXPOSURE. OUR BATTERY REVEALED A LARGE IMPACT ON MIRNA EXPRESSION PROFILING IN CELLS EXPOSED TO BOTH NMS. FROM THIS ANALYSIS, A SMALL SET OF FIVE MIRNAS (MIR-23A, MIR-25, MIR-96, MIR-210, AND MIR-502) WERE IDENTIFIED AS INFORMATIVE BIOMARKERS OF THE TRANSFORMING EFFECTS INDUCED BY NM EXPOSURES. THE USEFULNESS OF THIS REDUCED MIRNA BATTERY WAS FURTHER VALIDATED IN OTHER PREVIOUSLY GENERATED TRANSFORMED CELL SYSTEMS BY LONG-TERM EXPOSURE TO OTHER NMS (CONP, ZNONP, MSINP, AND CEO(2)NP). INTERESTINGLY, THE FIVE SELECTED MIRNAS WERE CONSISTENTLY OVEREXPRESSED IN ALL CELL LINES AND NMS TESTED. THESE RESULTS CONFIRM THE SUITABILITY OF THE PROPOSED SET OF MRNAS TO IDENTIFY THE POTENTIAL TRANSFORMING ABILITY OF NMS. PARTICULAR ATTENTION SHOULD BE PAID TO THE EPIGENOME AND ESPECIALLY TO MIRNAS FOR HAZARD ASSESSMENT OF NMS, AS WELLS AS FOR THE STUDY OF THE UNDERLYING MECHANISMS OF ACTION. 2021 4 4923 35 PARENTAL DIURON EXPOSURE CAUSES LOWER HATCHABILITY AND ABNORMAL OVARIAN DEVELOPMENT IN OFFSPRING OF MEDAKA (ORYZIAS MELASTIGMA). DIURON IS ONE OF THE MOST WIDELY USED HERBICIDES WORLDWIDE. IT HAS BEEN WIDELY DETECTED IN VARIOUS AQUATIC ENVIRONMENTS, ESPECIALLY IN MARINE ECOSYSTEMS. ALTHOUGH DIRECT EFFECTS OF DIURON EXPOSURE ON VARIOUS ORGANISMS HAVE BEEN REPORTED, LITTLE IS KNOWN ABOUT ITS EFFECTS ON MARINE FISHES INCLUDING MULTIGENERATIONAL EFFECTS. HEREIN, THE FILIAL GENERATION (F1) OF DIURON-EXPOSED MARINE MEDAKA (ORYZIAS MELASTIGMA) (F0) WAS RAISED IN CLEAN SEAWATER FROM FERTILIZED EGGS TO ADULTHOOD AND USED AS A MARINE FISH MODEL TO STUDY THE POTENTIAL MULTIGENERATIONAL EFFECTS OF DIURON. WE FOUND THAT THE SUCCESSFUL HATCHING OF F1 LARVAE WAS SIGNIFICANTLY REDUCED AND THAT OVARIAN DEVELOPMENT IN F1 FEMALES WAS RETARDED. A SIGNIFICANT INCREASE IN THE PERCENTAGE OF PREVITELLOGENIC OOCYTES, ALONG WITH A VISUAL DECREASE IN THE PERCENTAGE OF VITELLOGENIC AND MATURE OOCYTES IN THE F1 OVARY, WERE OBSERVED. THE HORMONE LEVELS OF THE HYPOTHALAMUS-PITUITARY-GONAD-LIVER AXIS AND VITELLOGENIN-RELATED TRANSCRIPTION WERE DOWNREGULATED. IN ADDITION, THE MRNA LEVELS OF DNA METHYLTRANSFERASE IN THE BRAIN, OVARY AND LIVER OF F1 ADULT FISH EXHIBITED SIGNIFICANT UPREGULATION, SUGGESTING THAT THE PROBABLE UNDERLYING MULTIGENERATIONAL MECHANISM MIGHT BE ASSOCIATED WITH EPIGENETIC MODIFICATIONS. TAKEN TOGETHER, THESE RESULTS DEMONSTRATED THAT CHRONIC ENVIRONMENTAL DIURON EXPOSURE IN F0 MARINE MEDAKA CAN INHIBIT F1 OVARY DEVELOPMENT AND SUGGESTED THAT DIURON MAY AFFECT MARINE FISH THRIVING IN THE OCEAN. 2022 5 903 32 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 6 865 37 CHRONIC ACRYLAMIDE EXPOSURE IN MALE MICE RESULTS IN ELEVATED DNA DAMAGE IN THE GERMLINE AND HERITABLE INDUCTION OF CYP2E1 IN THE TESTES. ACUTE ACRYLAMIDE EXPOSURE IN MALE RODENTS RESULTS IN REDUCED REPRODUCTIVE PERFORMANCE AND DOMINANT LETHALITY. HOWEVER, THE REPRODUCTIVE EFFECTS OF LOW DOSE CHRONIC EXPOSURE, WHICH BETTER REFLECTS THE NATURE OF HUMAN EXPOSURE, REMAIN FAR LESS CERTAIN. HUMAN DIETARY CONSUMPTION OF ACRYLAMIDE HAS BEEN ESTIMATED AT AN AVERAGE OF 1-4 MICROG/KG BW/DAY. IN ORDER TO SIMULATE THIS EXPOSURE, MALE MICE WERE PROVIDED WITH ACRYLAMIDE (1 MICROG/ML) VIA THEIR DRINKING WATER CONTINUOUSLY FOR SIX MONTHS, WHICH WAS EQUIVALENT TO A HUMAN DOSE OF 10.5 MICROG/ KG BW/DAY. THIS EXPOSURE REGIME INCREASED DNA DAMAGE IN THE SPERMATOZOA, WITHOUT AFFECTING A CONCOMITANT REDUCTION IN OVERALL FERTILITY. THE OFFSPRING OF ACRYLAMIDE TREATED MICE DID NOT HAVE AN INCREASED INCIDENCE OF SKIN PAPILLOMA FORMATION FOLLOWING THE TWO-STAGE TUMOR INDUCTION PROTOCOL. HOWEVER, THE MALE OFFSPRING OF ACRYLAMIDE TREATED FATHERS HAD SIGNIFICANTLY INCREASED LEVELS OF DNA DAMAGE IN THEIR SPERMATOZOA, DESPITE HAVING HAD NO DIRECT TOXICANT EXPOSURE. IT WAS ALSO FOUND THAT THE F0, AND MOST CRUCIALLY, F1 MICE HAD INCREASED LEVELS OF CYP2E1 PROTEIN IN THEIR GERM CELLS. THIS IS SIGNIFICANT AS CYP2E1 IS THE SOLE ENZYME RESPONSIBLE FOR CONVERSION OF ACRYLAMIDE TO ITS HARMFUL METABOLITE GLYCIDAMIDE. THIS ALTERED EXPRESSION MAY BE DUE TO EPIGENETIC ALTERATIONS. ADDITIONALLY, THE F0 AND F1 MICE HAD INCREASED OXIDATIVE ADDUCTS IN THE DNA OF THEIR GERM CELLS, WHICH WAS HYPOTHESIZED TO ARISE AS A BYPRODUCT OF INCREASED CYP2E1 ACTIVITY. THEREFORE, CHRONIC PATERNAL ACRYLAMIDE EXPOSURE IN MICE HAS CONSEQUENCES FOR THEIR OFFSPRING, AND RAISES CONCERNS FOR THE EFFECTS OF ACRYLAMIDE EXPOSURE IN THE HUMAN POPULATION AND THE ACCUMULATED EFFECTS WITH MULTIPLE GENERATIONS OF EXPOSURE. 2016 7 1819 26 EFFECTS OF CHRONIC OCHRATOXIN A EXPOSURE ON P53 HETEROZYGOUS AND P53 HOMOZYGOUS MICE. EXPOSURE TO THE MYCOTOXIN OCHRATOXIN A (OTA) CAUSES NEPHROPATHY IN DOMESTIC ANIMALS AND RODENTS AND RENAL TUMORS IN RODENTS AND POULTRY. HUMANS ARE EXPOSED TO OTA BY CONSUMING FOODS MADE WITH CONTAMINATED CEREAL GRAINS AND OTHER COMMODITIES. MANAGEMENT OF HUMAN HEALTH RISKS DUE TO OTA EXPOSURE DEPENDS, IN PART, ON ESTABLISHING A MODE OF ACTION (MOA) FOR OTA CARCINOGENESIS. TO FURTHER INVESTIGATE OTA'S MOA, P53 HETEROZYGOUS (P53+/-) AND P53 HOMOZYGOUS (P53+/+) MICE WERE EXPOSED TO OTA IN DIET FOR 26 WEEKS. THE FORMER ARE SUSCEPTIBLE TO TUMORIGENESIS UPON CHRONIC EXPOSURE TO GENOTOXIC CARCINOGENS. OTA-INDUCED RENAL DAMAGE BUT NO TUMORS WERE OBSERVED IN EITHER STRAIN, INDICATING THAT P53 HETEROZYGOSITY CONFERRED LITTLE ADDITIONAL SENSITIVITY TO OTA. RENAL CHANGES INCLUDED DOSE-DEPENDENT INCREASES IN CELLULAR PROLIFERATION, APOPTOSIS, KARYOMEGALY, AND TUBULAR DEGENERATION IN PROXIMAL TUBULES, WHICH WERE CONSISTENT WITH OCHRATOXICOSIS. THE LOWEST OBSERVED EFFECT LEVEL FOR RENAL CHANGES IN P53+/- AND P53+/+ MICE WAS 200 MUG OTA/KG BW/DAY. BASED ON THE LACK OF TUMORS AND THE SEVERITY OF RENAL AND BODY WEIGHT CHANGES AT A MAXIMUM TOLERATED DOSE, THE RESULTS WERE INTERPRETED AS SUGGESTIVE OF A PRIMARILY NONGENOTOXIC (EPIGENETIC) MOA FOR OTA CARCINOGENESIS IN THIS MOUSE MODEL. 2015 8 4939 31 PATERNAL NICOTINE EXPOSURE IN RATS PRODUCES LONG-LASTING NEUROBEHAVIORAL EFFECTS IN THE OFFSPRING. STUDIES OF INTERGENERATIONAL EFFECTS OF PARENTAL CHEMICAL EXPOSURE HAVE PRINCIPALLY FOCUSED ON MATERNAL EXPOSURE, PARTICULARLY FOR STUDIES OF ADVERSE NEUROBEHAVIORAL CONSEQUENCES ON THE OFFSPRING. MATERNAL NICOTINE EXPOSURE HAS LONG BEEN KNOWN TO CAUSE ADVERSE NEUROBEHAVIORAL EFFECTS ON THE OFFSPRING. HOWEVER, PATERNAL TOXICANT EXPOSURE HAS ALSO BEEN FOUND TO CAUSE NEUROBEHAVIORAL TOXICITY IN THEIR OFFSPRING. RECENT WORK SUGGESTS THAT PATERNAL NICOTINE EXPOSURE CAN HAVE EPIGENETIC EFFECTS, ALTHOUGH IT REMAINS UNCLEAR WHETHER SUCH CHANGES LEAD TO NEUROBEHAVIORAL EFFECTS. IN THE CURRENT STUDY, WE INVESTIGATED THE EFFECTS OF PATERNAL NICOTINE EXPOSURE ON NEUROBEHAVIORAL DEVELOPMENT OF THEIR OFFSPRING. MALE SPRAGUE-DAWLEY RATS WERE EXPOSED TO 0 OR 2 MG/KG/DAY NICOTINE (SC) FOR 56 CONSECUTIVE DAYS WITH TWO CONSECUTIVE 2ML4 OSMOTIC MINIPUMPS. FOLLOWING TREATMENT, THESE MALES WERE MATED WITH DRUG-NAIVE FEMALE RATS. OFFSPRING OF BOTH SEXES WERE TESTED IN A BEHAVIORAL BATTERY TO ASSESS LOCOMOTION, EMOTIONAL FUNCTION AND COGNITION. PATERNAL NICOTINE EXPOSURE DID NOT IMPACT OFFSPRING VIABILITY, HEALTH OR GROWTH. HOWEVER, BEHAVIORAL FUNCTION OF THE OFFSPRING WAS SIGNIFICANTLY ALTERED BY PATERNAL NICOTINE EXPOSURE. MALE OFFSPRING WITH PATERNAL NICOTINE EXPOSURE EXHIBITED LOCOMOTOR HYPERACTIVITY IN THE FIGURE-8 APPARATUS WHEN TESTED DURING ADOLESCENCE. WHEN RETESTED IN ADULTHOOD AND REGARDLESS OF SEX, OFFSPRING OF THE NICOTINE EXPOSED FATHER SHOWED SIGNIFICANTLY REDUCED HABITUATION OF LOCOMOTOR ACTIVITY OVER THE COURSE OF THE SESSION. COMPARED TO CONTROLS, FEMALE OFFSPRING OF NICOTINE-EXPOSED FATHERS SHOWED SIGNIFICANTLY REDUCED RESPONSE LATENCY IN THE RADIAL ARM MAZE TEST. IN ADDITION TO LOCOMOTOR HYPERACTIVITY, THE OFFSPRING OF NICOTINE-EXPOSED FATHERS ALSO SHOWED SIGNIFICANTLY DIMINISHED HABITUATION IN THE NOVEL OBJECT RECOGNITION TEST. THESE RESULTS INDICATE THAT CHRONIC PATERNAL NICOTINE EXPOSURE CAN IMPACT THE BEHAVIOR OF OFFSPRING, PRODUCING LOCOMOTOR HYPERACTIVITY AND IMPAIRED HABITUATION. 2019 9 1885 39 ENDOCRINE DISRUPTORS IN SOIL: EFFECTS OF BISPHENOL A ON GENE EXPRESSION OF THE EARTHWORM EISENIA FETIDA. XENOBIOTICS SUCH AS BISPHENOL A (BPA), ARE PRESENT IN BIOSOLIDS, WHICH ARE APPLIED AS ORGANIC FERTILIZERS IN AGRICULTURAL FIELDS. THEIR EFFECTS ON SOIL LIFE HAVE BEEN POORLY ASSESSED, AND THIS IS PARTICULARLY IMPORTANT IN THE CASE OF EARTHWORMS, WHICH REPRESENT THE MAIN ANIMAL BIOMASS IN THIS MEDIUM. IN THE PRESENT WORK WE STUDY THE IMPACTS OF BPA ON GENE EXPRESSION OF EISENIA FETIDA, A WIDELY USED ECOTOXICOLOGICAL MODEL. CHRONIC SOIL TESTS AND ACUTE CONTACT TESTS WERE PERFORMED, AND GENE EXPRESSION WAS ANALYZED IN TOTAL TISSUE AND IN MASCULINE REPRODUCTIVE ORGANS OF THE EARTHWORMS. THE GENES STUDIED IN THIS RESEARCH PLAYED A ROLE IN ENDOCRINE PATHWAYS, DETOXIFICATION MECHANISMS, STRESS RESPONSE, EPIGENETICS, AND GENOTOXICITY. MOST OF THE GENES WERE IDENTIFIED FOR THE FIRST TIME, PROVIDING POTENTIALLY USEFUL BIOMARKERS FOR FUTURE ASSESSMENTS. FOR CHRONIC EXPOSURES, NO CHANGES WERE DETECTED IN WHOLE-BODY TISSUE; HOWEVER, MASCULINE REPRODUCTIVE ORGANS SHOWED CHANGES IN THE EXPRESSION OF GENES RELATED TO ENDOCRINE FUNCTION (ECR, MAPR, ADIPOR), EPIGENETIC MECHANISMS (DNMTS), GENOTOXICITY (PARP1), AND STRESS RESPONSES (HSC70 4). FOR ACUTE EXPOSURES, THE EXPRESSION OF ONE EPIGENETIC-RELATED GENE WAS ALTERED FOR BOTH WHOLE-BODY TISSUES AND MALE REPRODUCTIVE ORGANS (PIWI2). FURTHER CHANGES WERE DETECTED FOR WHOLE-BODY TISSUES INVOLVED IN DETOXIFICATION (METALLOTHIONEIN), STRESS (HSC70 4), AND GENOTOXICITY (PARP1) MECHANISMS. ACUTE EXPOSURE EFFECTS WERE ALSO TESTED IN WHOLE-BODY TISSUES OF JUVENILES, SHOWING CHANGES IN THE EXPRESSION OF METALLOTHIONEIN AND PIWI2. THE MOLECULAR CHANGES FOUND IN THE ANALYZED EARTHWORMS INDICATE THAT EXPOSURE TO BPA MAY HAVE NEGATIVE IMPLICATIONS IN THEIR POPULATIONS. PARTICULARLY INTERESTING ARE THE ALTERATIONS RELATED TO EPIGENETIC MECHANISMS, WHICH SUGGEST THAT FUTURE GENERATIONS MAY BE IMPACTED. THIS STUDY IS THE FIRST TO EVALUATE THE MOLECULAR EFFECTS OF BPA ON SOIL ORGANISMS, AND FURTHER ASSAYS WILL BE NECESSARY TO BETTER CHARACTERIZE THE TRUE ENVIRONMENTAL REPERCUSSIONS. CAPSULE: LEVELS OF GENE EXPRESSION IN TOTAL-BODY TISSUES AND MASCULINE REPRODUCTIVE ORGANS WERE ANALYZED IN EARTHWORMS AFTER EXPOSURE TO BISPHENOL A AND WE OBSERVED ASSOCIATED CHANGES IN DETOXIFICATION, ENDOCRINE, EPIGENETIC, GENOTOXIC AND STRESS PATHWAYS. 2018 10 5367 24 RECENT ADVANCES IN SUNLIGHT-INDUCED CARCINOGENESIS USING THE XIPHOPHORUS MELANOMA MODEL. UNLIKE BREAST AND PROSTATE CANCERS, THE NATURE AND SEQUENCE OF CRITICAL GENETIC AND EPIGENETIC EVENTS INVOLVED IN THE INITIATION AND PROGRESSION OF MELANOMA ARE NOT WELL UNDERSTOOD. A CONTRIBUTING FACTOR TO THIS DILEMMA, ESPECIALLY GIVEN OUR CURRENT UNDERSTANDING OF THE IMPORTANCE OF UV LIGHT IN MELANOMA ETIOLOGY, IS THE LACK OF QUALITY UV-INDUCIBLE MELANOMA ANIMAL MODELS. IN THIS STUDY WE ELABORATE ON THE CAPABILITY OF UV LIGHT TO INDUCE CUTANEOUS MALIGNANT MELANOMAS (CMM) IN XIPHOPHORUS FISHES, WHICH WERE PREVIOUSLY FOUND TO DEVELOP MELANOMAS AFTER ACUTE NEONATAL UVB IRRADIATION. IN TWO SEPARATE TUMORIGENESIS EXPERIMENTS, WE EXPOSED ADULT XIPHOPHORUS HYBRIDS TO EITHER ACUTE UVB IRRADIATIONS (5 CONSECUTIVE DAILY TREATMENTS) OR CHRONIC SOLAR IRRADIATIONS (CONTINUOUS UVA/UVB TREATMENT FOR 9 MONTHS). ACUTE ADULT UVB IRRADIATION RESULTED IN THE SIGNIFICANT INDUCTION OF MELANOMAS, AND MOREOVER, THIS INDUCTION RATE IS EQUIVALENT TO THAT OF ANIMALS EXPOSED TO ACUTE NEONATAL UVB IRRADIATION. THIS STUDY REPRESENTS THE FIRST EVIDENCE THAT ACUTE ADULT UVB IRRADIATION, IN THE ABSENCE OF ANY EARLY LIFE EXPOSURES, INDUCES CMM. SIMILAR TO THE FINDINGS CONDUCTED ON OTHER DIVERGENT MELANOMA MODELS, INCLUDING HGF/SF TRANSGENIC MICE AND MONODELPHIS DOMESTICA, PROLONGED CHRONIC SOLAR UV WAS NOT A FACTOR IN MELANOMAGENESIS. 2012 11 122 23 A SYSTEMATIC REVIEW ON FLUORIDE-INDUCED EPIGENETIC TOXICITY IN MAMMALS. FLUORIDE, ONE OF THE GLOBAL GROUNDWATER CONTAMINANTS, IS UBIQUITOUS IN OUR DAY-TO-DAY LIFE FROM VARIOUS NATURAL AND ANTHROPOGENIC SOURCES. NUMEROUS IN VITRO, IN VIVO, AND EPIDEMIOLOGICAL STUDIES ARE CONDUCTED TO UNDERSTAND THE EFFECT OF FLUORIDE ON BIOLOGICAL SYSTEMS. A LOW CONCENTRATION OF FLUORIDE IS REPORTED TO INCREASE ORAL HEALTH, WHEREAS CHRONIC EXPOSURE TO HIGHER CONCENTRATIONS CAUSES FLUORIDE TOXICITY (FLUOROSIS). IT INCLUDES DENTAL FLUOROSIS, SKELETAL FLUOROSIS, AND FLUORIDE TOXICITY IN SOFT TISSUES. THE MECHANISM OF FLUORIDE TOXICITY HAS BEEN REVIEWED EXTENSIVELY. HOWEVER, EPIGENETIC REGULATION IN FLUORIDE TOXICITY HAS NOT BEEN REVIEWED. THIS SYSTEMATIC REVIEW SUMMARIZES THE CURRENT KNOWLEDGE REGARDING FLUORIDE-INDUCED EPIGENETIC TOXICITY IN THE IN VITRO, IN VIVO, AND EPIDEMIOLOGICAL STUDIES IN MAMMALIAN SYSTEMS. WE EXAMINED FOUR DATABASES FOR THE ASSOCIATION BETWEEN EPIGENETICS AND FLUORIDE EXPOSURE. OUT OF 932 ARTICLES (AS OF 31 MARCH 2022), 39 MET OUR INCLUSION CRITERIA. MOST OF THE STUDIES FOCUSED ON DIFFERENT GENES, AND OVERALL, PRELIMINARY EVIDENCE FOR EPIGENETIC REGULATION OF FLUORIDE TOXICITY WAS IDENTIFIED. WE FURTHER HIGHLIGHT THE NEED FOR EPIGENOME STUDIES RATHER THAN CANDIDATE GENES AND PROVIDE RECOMMENDATIONS FOR FUTURE RESEARCH. OUR RESULTS INDICATE A CORRELATION BETWEEN FLUORIDE EXPOSURE AND EPIGENETIC PROCESSES. FURTHER STUDIES ARE WARRANTED TO ELUCIDATE AND CONFIRM THE MECHANISM OF EPIGENETIC ALTERATIONS MEDIATED FLUORIDE TOXICITY. 2022 12 6553 30 TRANSGENERATIONAL EFFECTS IN DNA METHYLATION, GENOTOXICITY AND REPRODUCTIVE PHENOTYPE BY CHRONIC ARSENIC EXPOSURE. AN EMERGING CONCERN IS THE INFLUENCES OF EARLY LIFE EXPOSURE TO ENVIRONMENTAL TOXICANTS ON OFFSPRING CHARACTERISTICS IN LATER LIFE. SINCE RECENT EVIDENCE SUGGESTS A TRANSGENERATIONAL TRANSFERENCE OF ABERRANT PHENOTYPES FROM EXPOSED-PARENTS TO NON-EXPOSED OFFSPRING RELATED TO ADULT-ONSET DISEASES INCLUDING REPRODUCTIVE PHENOTYPE. THE TRANSGENERATIONAL POTENTIAL OF ARSENIC A WELL KNOW GENOTOXIC AND EPIGENETIC MODIFIER AGENT HAS NOT BEEN ASSESSED IN MAMMALS UNTIL NOW. IN THIS EXPERIMENTAL STUDY, WE EVALUATED THE TRANSGENERATIONAL EFFECTS OF ARSENIC IN A RAT MODEL WITH CHRONIC EXPOSURE TO ARSENIC. RATS CHRONICALLY EXPOSED TO ARSENIC IN DRINKING WATER (1 MG AS(2)O(3)/ML) (F0) WERE MATED TO PRODUCE THE ARSENIC LINEAGE (F1, F2, AND F3). THE ARSENIC TOXIC EFFECTS ON WERE EVALUATED OVER THE FOUR GENERATIONS BY ANALYZING THE DNA METHYLATION PERCENTAGE, GENOTOXICITY IN WBC AND PHYSICAL AND REPRODUCTIVE PARAMETERS, INCLUDING SPERM QUALITY PARAMETERS AND HISTOPATHOLOGICAL EVALUATION OF THE GONADS. CHRONIC EXPOSURE TO ARSENIC CAUSED GENOTOXIC DAMAGE (F0-F3) DIFFERENT METHYLATION PATTERNS, ALTERATIONS IN PHYSICAL AND REPRODUCTIVE PARAMETERS, ABERRANT MORPHOLOGY IN THE OVARIES (F0 AND F1) AND TESTICLES (F1-F3), AND A DECREASE IN THE QUALITY OF SPERM (F0-F3, EXCEPT F2). PARENTAL CHRONIC ARSENIC EXPOSURE CAUSES TRANSGENERATIONAL GENOTOXICITY AND CHANGES IN GLOBAL DNA METHYLATION WHICH MIGHT BE ASSOCIATED WITH REPRODUCTIVE DEFECTS IN RATS. COMBINED WITH RECENT STUDIES REVEAL THAT DISTURBANCES IN THE EARLY LIFE OF AN INDIVIDUAL CAN AFFECT THE HEALTH OF LATER GENERATIONS. 2021 13 4009 34 LOW LEVELS OF CD INDUCE PERSISTING EPIGENETIC MODIFICATIONS AND ACCLIMATION MECHANISMS IN THE EARTHWORM LUMBRICUS TERRESTRIS. TOXIC EFFECTS OF CADMIUM (CD), A COMMON SOIL POLLUTANT, ARE STILL NOT VERY WELL UNDERSTOOD, PARTICULARLY IN REGARD TO ITS EPIGENETIC IMPACT. THEREFORE, THE AIM OF THIS STUDY WAS TO ASSESS DNA METHYLATION CHANGES AND THEIR PERSISTENCE IN THE EARTHWORM LUMBRICUS TERRESTRIS UPON CHRONIC LOW DOSE CD EXPOSURE USING METHYLATION SENSITIVE AMPLIFICATION POLYMORPHISM (MSAP). MOREOVER, THE BIOMARKER RESPONSE AND FITNESS OF THE EARTHWORMS, AS WELL AS THE EXPRESSION OF DETOXIFICATION-RELATED GENES (METALLOTHIONEIN (MT) AND PHYTOCHELATIN SYNTHASE (PCS)) WAS EVALUATED. LOW LEVELS OF CD CAUSED AN INCREASE IN GENOME-WIDE DNA METHYLATION, WHICH REMAINED PARTLY MODIFIED, EVEN AFTER SEVERAL MONTHS OF RECOVERY IN UNPOLLUTED SOIL. INCREASED CELLULAR STRESS SEEMED TO DECREASE AFTER TWO WEEKS OF EXPOSURE WHEREAS FITNESS PARAMETERS REMAINED UNAFFECTED BY CD, PROBABLY AS A RESULT FROM THE ACTIVATION OF DETOXIFICATION MECHANISMS LIKE THE EXPRESSION OF MTS. INTERESTINGLY, EVEN THOUGH THE LEVEL OF CD EXPOSURE WAS VERY LOW, MT EXPRESSION LEVELS INDICATE THE DEVELOPMENT OF ACCLIMATION MECHANISMS. TAKEN TOGETHER, THIS STUDY DEMONSTRATES THAT ACCLIMATION, AS WELL AS EPIGENETIC MODIFICATIONS CAN OCCUR ALREADY IN MODERATELY POLLUTED ENVIRONMENTS. IN ADDITION, THESE EFFECTS CAN HAVE LONG-LASTING IMPACTS ON KEY SPECIES OF SOIL INVERTEBRATES AND MIGHT PERSIST LONG AFTER THE ACTUAL HEAVY METAL CHALLENGE HAS PASSED. 2017 14 5077 22 PHYSIOLOGICAL PATHWAYS TO RAPID PROSOCIAL EVOLUTION. DOGS (CANIS LUPUS FAMILIARIS) DESCEND FROM WOLVES (CANIS LUPUS) SHARING THE SAME ECOLOGICAL NICHE OF COOPERATIVE HUNTERS, AS HUMANS. INITIALLY, HUMANS AND WOLVES WERE COMPETITORS STARTING INTERSPECIFIC COMMUNICATION IN ORDER TO AVOID RISK OF INJURY. THE EVOLUTIONARY CONTINUITY OF MAMMALIAN BRAINS ENABLED INTERSPECIFIC PROSOCIAL CONTACTS BETWEEN BOTH OF THEM, WHICH REDUCED STRESS, AND ENABLED BEHAVIORAL CULTURES LEADING TO GENETIC ISOLATION OF THOSE WOLVES. DOGS ARE THE FIRST DOMESTICATED ANIMAL LIVING TOGETHER WITH HUMANS FOR ABOUT 25,000 YEARS. DOMESTICATION MEANS DECREASED AGGRESSION AND FLIGHT DISTANCE TOWARD HUMANS, THUS CHANGES IN THE STRESS AXIS ARE CRUCIAL. THE HYPOTHESIS OF ACTIVE SOCIAL DOMESTICATION CONSIDERS GENETIC SELECTION AS A NECESSARY PREDICTION BUT NOT A SUFFICIENT EXPLANATION OF DOG DOMESTICATION. IN ADDITION, DOG DOMESTICATION IS SUGGESTED TO BE AN EPIGENETIC DISCLOSURE. DUE TO CHANGED STRESS ACTIVITY, EPIGENETIC MECHANISMS AFFECT CEREBRAL RECEPTOR ACTIVITY AND REGULATE TRANSPOSON EXPRESSIONS, THUS SHAPING BRAIN FUNCTION AND BEHAVIOR. INTERSPECIFIC PROSOCIAL CONTACTS INITIATED VIA SEROTONIN RELEASE AN ENZYMATIC CASCADE ENHANCING, EPIGENETI-CALLY, THE GLUCOCORTICOID NEGATIVE FEEDBACK LOOP. REDUCED CHRONIC STRESS IMPROVED SOCIAL LEARNING CAPABILITY AND INHIBITORY CONTROL. OVER TIME, THOSE WOLVES COULD INTEGRATE THEMSELVES INTO HUMAN SOCIAL STRUCTURES, THUS BECOMING DOGS. IN ANALOGY, HUMAN MENTAL SKILLS, SUCH AS CREATING ART AND CULTURE, MIGHT HAVE ALSO IMPROVED DURING THE UPPER PALEOLITHIC. 2019 15 5616 32 SAMUL-TANG AMELIORATES OOCYTE DAMAGE DUE TO CYCLOPHOSPHAMIDE-INDUCED CHRONIC OVARIAN DYSFUNCTION IN MICE. SAMUL-TANG (SM), A TRADITIONAL HERBAL MEDICINE, HAS BEEN USED TO TREAT MENSTRUAL IRREGULARITIES AND INFERTILITY IN WOMEN. HOWEVER, THE CELLULAR AND MOLECULAR MECHANISMS UNDERLYING THE EFFECTS OF SM REMAIN ELUSIVE. WE INVESTIGATED THE POTENTIAL PROTECTIVE EFFECT OF SM AGAINST CHRONIC OVARIAN DYSFUNCTION AND USED BIOINFORMATICS ANALYSIS TO IDENTIFY ITS UNDERLYING MECHANISM IN A MOUSE MODEL OF CYCLOPHOSPHAMIDE (CP)-INDUCED DIMINISHED OVARIAN RESERVE. FEMALE C57BL/6 MICE WERE INTRAPERITONEALLY INJECTED WITH CP THREE TIMES A WEEK, FOLLOWED BY ORAL ADMINISTRATION OF DISTILLED WATER (CP GROUP) OR SM (CP + SM GROUP) FOR 4 WEEKS. FOUR WEEKS LATER, THE EFFECT OF SM WAS ASSESSED BY OVARIAN TISSUE HISTOLOGICAL ANALYSIS, STEROID HORMONE MEASUREMENT, OOCYTE QUALITY, AND MRNA AND MICRORNA MICROARRAY ANALYSIS IN THE OVARIES. ALTHOUGH SM ADMINISTRATION DID NOT PREVENT CP-INDUCED FOLLICLE LOSS IN MICE, THE QUALITY OF OOCYTES WAS BETTER IN CP + SM MICE THAN IN CP MICE. GENE EXPRESSION ANALYSIS REVEALED THAT THE EXPRESSION OF FERTILISATION- AND OVARIAN FOLLICLE DEVELOPMENT-RELATED GENES WAS ALTERED BY CP TREATMENT BUT NORMALIZED AFTER SM ADMINISTRATION. FURTHER BIOINFORMATICS ANALYSIS SHOWED POSSIBLE INTERACTIONS BETWEEN DIFFERENTIALLY EXPRESSED MRNAS AND MICRORNAS. THEREFORE, WE DEMONSTRATED THE PROTECTIVE EFFECTS OF SM ON OVARIAN FUNCTION AND OOCYTE MATURATION AGAINST CP-INDUCED DAMAGE VIA MULTIPLE EPIGENETIC MECHANISMS. 2020 16 3614 25 IN VITRO CELL TRANSFORMATION ASSAYS: A VALUABLE APPROACH FOR CARCINOGENIC POTENTIALITY ASSESSMENT OF NANOMATERIALS. THIS REVIEW EXPLORES THE APPLICATION OF IN VITRO CELL TRANSFORMATION ASSAYS (CTAS) AS A SCREENING PLATFORM TO ASSESS THE CARCINOGENIC POTENTIAL OF NANOMATERIALS (NMS) RESULTING FROM CONTINUOUSLY GROWING INDUSTRIAL PRODUCTION AND USE. THE WIDESPREAD APPLICATION OF NMS IN VARIOUS FIELDS HAS RAISED CONCERNS ABOUT THEIR POTENTIAL ADVERSE EFFECTS, NECESSITATING SAFETY EVALUATIONS, PARTICULARLY IN LONG-TERM CONTINUOUS EXPOSURE SCENARIOS. CTAS PRESENT A REALISTIC SCREENING PLATFORM FOR KNOWN AND EMERGING NMS BY EXAMINING THEIR RESEMBLANCE TO THE HALLMARK OF MALIGNANCY, INCLUDING HIGH PROLIFERATION RATES, LOSS OF CONTACT INHIBITION, THE GAIN OF ANCHORAGE-INDEPENDENT GROWTH, CELLULAR INVASION, DYSREGULATION OF THE CELL CYCLE, APOPTOSIS RESISTANCE, AND ABILITY TO FORM TUMORS IN EXPERIMENTAL ANIMALS. THROUGH THE DELIBERATE TRANSFORMATION OF CELLS VIA CHRONIC NM EXPOSURE, RESEARCHERS CAN INVESTIGATE THE TUMORIGENIC PROPERTIES OF NMS AND THE UNDERLYING MECHANISMS OF CANCER DEVELOPMENT. THIS ARTICLE EXAMINES NM-INDUCED CELL TRANSFORMATION STUDIES, FOCUSING ON IDENTIFYING EXISTING KNOWLEDGE GAPS. SPECIFICALLY, IT EXPLORES THE PHYSICOCHEMICAL PROPERTIES OF NMS, EXPERIMENTAL MODELS, ASSAYS, DOSE AND TIME REQUIREMENTS FOR CELL TRANSFORMATION, AND THE UNDERLYING MECHANISMS OF MALIGNANCY. OUR REVIEW AIMS TO ADVANCE UNDERSTANDING IN THIS FIELD AND IDENTIFY AREAS FOR FURTHER INVESTIGATION. 2023 17 4538 34 MULTISCALE APPROACH TO DECIPHERING THE MOLECULAR MECHANISMS INVOLVED IN THE DIRECT AND INTERGENERATIONAL EFFECT OF IBUPROFEN ON MOSQUITO AEDES AEGYPTI. THE ANTI-INFLAMMATORY IBUPROFEN IS A UBIQUITOUS SURFACE WATER CONTAMINANT. HOWEVER, THE CHRONIC IMPACT OF THIS PHARMACEUTICAL ON AQUATIC INVERTEBRATE POPULATIONS REMAINS POORLY UNDERSTOOD. IN MODEL INSECT AEDES AEGYPTI, WE INVESTIGATED THE INTERGENERATIONAL CONSEQUENCES OF PARENTAL CHRONIC EXPOSURE TO AN ENVIRONMENTALLY RELEVANT CONCENTRATION OF IBUPROFEN. WHILE EXPOSED INDIVIDUALS DID NOT SHOW ANY PHENOTYPIC CHANGES, THEIR PROGENY SHOWED ACCELERATED DEVELOPMENT AND AN INCREASED TOLERANCE TO STARVATION. IN ORDER TO UNDERSTAND THE MECHANISTIC PROCESSES UNDERPINNING THE DIRECT AND INTERGENERATIONAL IMPACTS OF IBUPROFEN, WE COMBINED TRANSCRIPTOMIC, METABOLOMICS, AND HORMONE KINETICS STUDIES AT SEVERAL LIFE STAGES IN EXPOSED INDIVIDUALS AND THEIR PROGENY. THIS INTEGRATIVE APPROACH REVEALED MODERATE TRANSCRIPTIONAL CHANGES IN EXPOSED LARVAE CONSISTENT WITH THE PHARMACOLOGICAL MODE OF ACTION OF IBUPROFEN. PARENTAL EXPOSURE LED TO LOWER LEVELS OF SEVERAL POLAR METABOLITES IN PROGENY EGGS AND TO MAJOR TRANSCRIPTIONAL CHANGES IN THE FOLLOWING LARVAL STAGE. THESE TRANSCRIPTIONAL CHANGES, MOST LIKELY DRIVEN BY CHANGES IN THE EXPRESSION OF NUMEROUS TRANSCRIPTION FACTORS AND EPIGENETIC REGULATORS, LED TO ECDYSONE SIGNALING AND STRESS RESPONSE POTENTIATION. OVERALL, THE PRESENT STUDY ILLUSTRATES THE COMPLEXITY OF THE MOLECULAR BASIS OF THE INTERGENERATIONAL POLLUTANT RESPONSE IN INSECTS AND THE IMPORTANCE OF CONSIDERING THE ENTIRE LIFE CYCLE OF EXPOSED ORGANISMS AND OF THEIR PROGENY IN ORDER TO FULLY UNDERSTAND THE MODE OF ACTION OF POLLUTANTS AND THEIR IMPACT ON ECOSYSTEMS. 2018 18 907 34 CHRONIC EXPOSURE TO ENVIRONMENTALLY RELEVANT CONCENTRATION OF FLUORIDE ALTERS OGG1 AND RAD51 EXPRESSIONS IN MICE: INVOLVEMENT OF EPIGENETIC REGULATION. CHRONIC EXPOSURE TO FLUORIDE (F) BEYOND THE PERMISSIBLE LIMIT (1.5 PPM) IS KNOWN TO CAUSE DETRIMENTAL HEALTH EFFECTS BY INDUCTION OF OXIDATIVE STRESS-MEDIATED DNA DAMAGE OVERPOWERING THE DNA REPAIR MACHINERY. IN THE PRESENT STUDY, WE ASSESSED F INDUCED OXIDATIVE STRESS THROUGH MONITORING BIOCHEMICAL PARAMETERS AND LOOKED INTO THE EFFECT OF CHRONIC F EXPOSURE ON TWO CRUCIAL DNA REPAIR GENES OGG1 AND RAD51 HAVING IMPORTANT ROLE AGAINST ROS INDUCED DNA DAMAGES. TO ADDRESS THIS ISSUE, WE EXPOSED SWISS ALBINO MICE TO AN ENVIRONMENTALLY RELEVANT CONCENTRATION OF FLUORIDE (15 PPM NAF) FOR 8 MONTHS. RESULTS REVEALED HISTOARCHITECTURAL DAMAGES IN LIVER, BRAIN, KIDNEY AND SPLEEN. DEPLETION OF GSH, INCREASE IN LIPID PEROXIDATION AND CATALASE ACTIVITY IN LIVER AND BRAIN CONFIRMED THE GENERATION OF OXIDATIVE STRESS. QRT-PCR RESULT SHOWED THAT EXPRESSIONS OF OGG1 AND RAD51 WERE ALTERED AFTER F EXPOSURE IN THE AFFECTED ORGANS. PROMOTER HYPERMETHYLATION WAS ASSOCIATED WITH THE DOWNREGULATION OF RAD51. F-INDUCED DNA DAMAGE AND THE COMPROMISED DNA REPAIR MACHINERY TRIGGERED INTRINSIC PATHWAY OF APOPTOSIS IN LIVER AND BRAIN. THE PRESENT STUDY INDICATES THE POSSIBLE ASSOCIATION OF EPIGENETIC REGULATION WITH F INDUCED NEUROTOXICITY. 2020 19 227 40 ADAPTATION OF AN OUTBREAKING INSECT DEFOLIATOR TO CHRONIC NUTRITIONAL STRESS. DURING INSECT OUTBREAKS, THE HIGH NUMBER OF INDIVIDUALS FEEDING ON ITS HOST PLANT CAUSES A DEPLETION OF THE FOOD SOURCE. REDUCED AVAILABILITY AND DECREASED QUALITY OF NUTRIENTS NEGATIVELY INFLUENCE LIFE-HISTORY TRAITS OF INSECTS DRIVING THEM TO DEVELOP ADAPTIVE STRATEGIES TO PERSIST IN THE ENVIRONMENT. IN A LABORATORY EXPERIMENT WITH THREE REPETITIONS, WE TESTED THE EFFECT OF CHRONIC NUTRITIONAL STRESS ON SPRUCE BUDWORM PERFORMANCE DURING THREE GENERATIONS TO DETERMINE THE ADAPTIVE STRATEGIES EMPLOYED BY THE INSECT TO DEAL WITH A SELECTION PRESSURE PRODUCED BY LOW-QUALITY DIET. OUR RESULTS SHOW THAT ALL TESTED LIFE-HISTORY TRAITS (MORTALITY, DEVELOPMENTAL TIME, PUPAL MASS, GROWTH RATE AND FEMALE FECUNDITY) BUT FEMALE FERTILITY WERE NEGATIVELY INFLUENCED BY THE LOW-QUALITY DIET SIMULATING FOOD DEPLETION DURING OUTBREAK CONDITIONS. HOWEVER, ESPECIALLY FEMALES IN THE THIRD GENERATION UNDER CHRONIC NUTRITIONAL STRESS SHOW AN ADAPTIVE RESPONSE IN LIFE-HISTORY TRAITS WHEN COMPARED TO THOSE REARED ONLY ONE GENERATION ON LOW-QUALITY DIET. LARVAL DEVELOPMENTAL TIME SIGNIFICANTLY DECREASED AND PUPAL MASS, GROWTH RATE AND FECUNDITY SIGNIFICANTLY INCREASED. THE STUDY DEMONSTRATES THE CAPACITY OF SPRUCE BUDWORM TO REACT TO CHRONIC NUTRITIONAL STRESS WITH ADAPTATIONS THAT MAY BE CAUSED BY EPIGENETIC PARENTAL EFFECTS. THIS INFORMATION CAN HELP TO UNDERSTAND THE COURSE OF AN OUTBREAK ESPECIALLY AT PEAK DENSITIES AND DURING THE COLLAPSE. 2015 20 6555 30 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