1 759 185 CASE REPORT OF CUTANEOUS SQUAMOUS CELL CARCINOMA AT THE WRIST JOINT AND THE PUBLIC HEALTH CRISIS OF ARSENICOSIS. CONTEXT: ARSENICOSIS IS CAUSED BY LONG TERM (6 MONTHS PLUS) INGESTION OF ARSENIC ABOVE A SAFE DOSE, CHARACTERIZED BY SKIN LESIONS AND POSSIBLE INVOLVEMENT OF INTERNAL ORGANS. ARSENICOSIS IS COMMON IN INDIA AND BANGLADESH WHERE NATURALLY OCCURRING HIGH CONCENTRATIONS OF ARSENIC IN THE EARTH'S CRUST CONTAMINATE GROUND WATER, CAUSING ADVERSE HEALTH EFFECTS. CASE PRESENTATION: WE REPORT A CASE OF A 55-YEAR-OLD INDIAN MALE, RESIDENT OF A KNOWN ARSENIC ENDEMIC REGION OF UTTAR PRADESH WHO SUFFERED FROM CHARACTERISTIC PULMONARY AND CUTANEOUS FEATURES OF CHRONIC ARSENIC TOXICITY WHICH INCLUDED RADIOLOGICAL FINDINGS OF INTERSTITIAL LUNG DISEASE, HYPERKERATOTIC LESIONS OVER THE PALMS AND SOLES, RAIN DROP LIKE PIGMENTATION OVER THE TRUNK, AND CARCINOMATOUS CHANGES AT THE WRIST JOINT. THE PATIENT WAS STARTED ON CHELATING AGENTS (D-PENICILLAMINE) AND ORAL RETINOIDS (ISOTRETINOIN) FOLLOWED BY THE SURGICAL EXCISION OF THE CARCINOMA. DISCUSSION: ENVIRONMENTAL CONTAMINATION WITH ARSENIC IS A WELL-KNOWN HEALTH HAZARD IN SOUTH ASIAN COUNTRIES. THE MAIN SOURCE IS CONSUMPTION OF CONTAMINATED GROUND WATER FOR DOMESTIC PURPOSES. CUTANEOUS LESIONS, INTERNAL ORGAN INVOLVEMENT INCLUDING INTERSTITIAL LUNG DISEASE AND CARCINOMAS AS OBSERVED IN OUR PATIENT HAVE BEEN REPORTED IN THE LITERATURE. VARIOUS MECHANISMS LIKE EPIGENETIC CHANGES AND ARSENIC-INDUCED IMMUNE SUPPRESSION HAVE BEEN PROPOSED FOR THE DEVELOPMENT OF CUTANEOUS CARCINOMAS WITH PROLONGED EXPOSURE TO ARSENIC. RELEVANCE TO CLINICAL PRACTICE: AMONG THE VARIOUS CAUSES OF PALMO-PLANTAR HYPERKERATOSIS, ARSENICOSIS SHOULD BE KEPT IN MIND WHEN PRESENTING IN COMBINATION WITH PIGMENTARY CHANGES AND CARCINOMATOUS GROWTH FROM AN ARSENIC-ENDEMIC REGION. CONCLUSIONS: PEOPLE RESIDING IN ARSENIC-ENDEMIC REGIONS SHOULD BE MADE AWARE OF ARSENIC-RELATED HEALTH HAZARDS. RAINWATER HARVESTING AND GOOD NUTRITION ARE THE SIMPLEST MEASURES WHICH COULD BE ADOPTED BY THE EXPOSED POPULATION IN AFFECTED AREAS. SEVERAL METHODS HAVE ALSO BEEN EMPLOYED BY GOVERNMENTAL AND NON-GOVERNMENT ORGANIZATIONS TO SEPARATE ARSENIC FROM CONTAMINATED WATER TO COMBAT ARSENIC-RELATED DISEASES AND CARCINOMAS. COMPETING INTERESTS: THE AUTHORS DECLARE NO COMPETING FINANCIAL INTERESTS. 2021 2 876 39 CHRONIC ARSENIC INTOXICATION DIAGNOSTIC SCORE (CASIDS). ARSENIC AND ITS COMPOUNDS ARE WELL-ESTABLISHED, POTENT, ENVIRONMENTALLY WIDESPREAD AND PERSISTENT TOXICANTS WITH METABOLIC, GENOTOXIC, MUTAGENIC, TERATOGENIC, EPIGENETIC AND CARCINOGENIC EFFECTS. ARSENIC OCCURS NATURALLY IN THE EARTH'S CRUST, BUT ANTHROPOGENIC ARSENIC EMISSIONS HAVE SURMOUNTED THE EMISSIONS FROM IMPORTANT NATURAL SOURCES SUCH AS VOLCANISM. INORGANIC ARSENICALS EXHIBIT ACUTE AND CHRONIC TOXICITIES IN VIRTUALLY ALL CELL TYPES AND TISSUES, AND HENCE ARSENIC INTOXICATION AFFECTS MULTIPLE SYSTEMS. WHEREAS ACUTE ARSENIC INTOXICATION IS RARE AND RELATIVELY EASY TO DIAGNOSE, CHRONIC ARSENIC INTOXICATION (CASI) IS COMMON BUT GOES OFTEN MISDIAGNOSED. BASED ON A REVIEW OF THE LITERATURE AS WELL AS OUR OWN CLINICAL EXPERIENCE, WE PROPOSE A CHRONIC ARSENIC INTOXICATION DIAGNOSTIC SCORE (CASIDS). A DISTINCTIVE FEATURE OF CASIDS IS THE USE OF BONE ARSENIC LOAD AS AN ESSENTIAL CRITERION FOR THE INDIVIDUAL RISK ASSESSMENT OF CHRONIC ARSENIC INTOXICATION, COMBINED WITH A SYSTEMIC CLINICAL ASSESSMENT. WE PRESENT CLINICAL EXAMPLES WHERE CASIDS IS APPLIED FOR THE DIAGNOSIS OF CASI, REVIEW THE MAIN TOPICS OF THE TOXICITY OF ARSENIC IN DIFFERENT CELL AND ORGAN SYSTEMS AND DISCUSS THE THERAPY AND PREVENTION OF DISEASE CAUSED OR AGGRAVATED BY CHRONIC ARSENIC INTOXICATION. CASIDS CAN HELP PHYSICIANS ESTABLISH THE DIAGNOSIS OF CASI AND ASSOCIATED CONDITIONS. 2018 3 2603 37 EPIGENETICS, ENVIRONMENT AND EPIDEMIOLOGY: AN INTERVIEW WITH KARL KELSEY. IN THIS INTERVIEW, PROFESSOR KARL KELSEY SPEAKS WITH STORM JOHNSON, COMMISSIONING EDITOR FOR EPIGENOMICS, ON HIS WORK TO DATE IN THE FIELD OF ENVIRONMENTAL EPIGENOMICS AND EPIDEMIOLOGY. DR KARL KELSEY, MD, MOH IS A PROFESSOR OF EPIDEMIOLOGY AND PATHOLOGY AND LABORATORY MEDICINE AT BROWN UNIVERSITY. HE IS THE FOUNDING DIRECTOR OF THE CENTER FOR ENVIRONMENTAL HEALTH AND TECHNOLOGY AND HEAD OF THE ENVIRONMENTAL HEALTH SECTION AT THE DEPARTMENT OF EPIDEMIOLOGY. DR KELSEY IS INTERESTED IN THE APPLICATION OF LABORATORY-BASED BIOMARKERS IN ENVIRONMENTAL DISEASE, WITH EXPERIENCE IN CHRONIC DISEASE EPIDEMIOLOGY AND TUMOR BIOLOGY. THE GOALS OF HIS WORK INCLUDE A MECHANISTIC UNDERSTANDING OF INDIVIDUAL SUSCEPTIBILITY TO EXPOSURE-RELATED CANCERS. IN ADDITION, HIS LABORATORY IS INTERESTED IN TUMOR BIOLOGY, INVESTIGATING SOMATIC ALTERATIONS IN TUMOR TISSUE FROM THE PATIENTS WHO HAVE DEVELOPED EXPOSURE-RELATED CANCERS. THIS WORK INVOLVES THE USE OF AN EPIDEMIOLOGIC APPROACH TO CHARACTERIZE EPIGENETIC AND GENETIC ALTERATION OF GENES IN THE CAUSAL PATHWAY FOR MALIGNANCY. ACTIVE WORK INCLUDES SEVERAL STUDIES OF INDIVIDUAL SUSCEPTIBILITY TO CANCER. DR KELSEY'S LABORATORY MAINLY INVESTIGATES SUSCEPTIBILITY TO SMOKING-RELATED LUNG CANCER AND STUDIES MULTI-RACIAL AND ETHNIC POPULATIONS. IN ADDITION, THE LABORATORY IS ALSO INVOLVED WITH THE STUDY OF INHERITED SUSCEPTIBILITY TO BRAIN TUMORS AND PANCREATIC CANCER. MAJOR CASE CONTROL STUDIES THAT ARE ONGOING IN THE LABORATORY INCLUDE STUDIES DESIGNED TO UNDERSTAND INHERITED AND ACQUIRED SUSCEPTIBILITY IN HEAD AND NECK CANCERS. THE LABORATORY IS ALSO INVOLVED IN A CASE CONTROL STUDY OF ASBESTOS-ASSOCIATED MESOTHELIOMA, ARSENIC EXPOSURE, CIGARETTE SMOKING AND BLADDER CANCER. CONSIDERABLE WORK IS BEING DEVOTED TO UNDERSTANDING THE MECHANISMS OF ACTION OF BOTH ASBESTOS AND ARSENIC INCLUDING THEIR ABILITY TO AFFECT PROMOTER METHYLATION AND GENE SILENCING IN CARCINOGENESIS. RECENT LABORATORY STUDIES INCLUDES AN INTEREST IN USING NEWLY DEVELOPED DNA METHYLATION BIOMARKERS TO PROBE IMMUNE PROFILES FROM ARCHIVED BLOOD. DR KELSEY RECEIVED HIS MD FROM THE UNIVERSITY OF MINNESOTA AND MASTERS OF OCCUPATIONAL HEALTH FROM HARVARD UNIVERSITY. 2022 4 4155 37 MECHANISTIC UNDERSTANDING OF THE TOXIC EFFECTS OF ARSENIC AND WARFARE ARSENICALS ON HUMAN HEALTH AND ENVIRONMENT. WORLDWIDE, MORE THAN 200 MILLION PEOPLE ARE ESTIMATED TO BE EXPOSED TO UNSAFE LEVELS OF ARSENIC. CHRONIC EXPOSURE TO UNSAFE LEVELS OF GROUNDWATER ARSENIC IS RESPONSIBLE FOR MULTIPLE HUMAN DISORDERS, INCLUDING DERMAL, CARDIOVASCULAR, NEUROLOGICAL, PULMONARY, RENAL, AND METABOLIC CONDITIONS. CONSUMPTION OF RICE AND SEAFOOD (WHERE HIGH LEVELS OF ARSENIC ARE ACCUMULATED) IS ALSO RESPONSIBLE FOR HUMAN EXPOSURE TO ARSENIC. THE TOXICITY OF ARSENIC COMPOUNDS VARIES GREATLY AND MAY DEPEND ON THEIR CHEMICAL FORM, SOLUBILITY, AND CONCENTRATION. SURPRISINGLY, SYNTHETIC ORGANOARSENICALS ARE EXTREMELY TOXIC MOLECULES WHICH CREATED INTEREST IN THEIR DEVELOPMENT AS CHEMICAL WARFARE AGENTS (CWAS) DURING WORLD WAR I (WWI). AMONG THESE CWAS, ADAMSITE, CLARK I, CLARK II, AND LEWISITE ARE OF CRITICAL IMPORTANCE, AS STOCKPILES OF THESE AGENTS STILL EXIST WORLDWIDE. IN ADDITION, UNUSED WWII WEAPONIZED ARSENICALS DISCARDED IN WATER BODIES OR BURIED IN MANY PARTS OF THE WORLD CONTINUE TO POSE A SERIOUS THREAT TO THE ENVIRONMENT AND HUMAN HEALTH. METABOLIC INHIBITION, OXIDATIVE STRESS, GENOTOXICITY, AND EPIGENETIC ALTERATIONS INCLUDING MICRO-RNA-DEPENDENT REGULATION ARE SOME OF THE UNDERLYING MECHANISMS OF ARSENIC TOXICITY. MECHANISTIC UNDERSTANDING OF THE TOXICITY OF ORGANOARSENICALS IS ALSO CRITICAL FOR THE DEVELOPMENT OF EFFECTIVE THERAPEUTIC INTERVENTIONS. THIS REVIEW PROVIDES COMPREHENSIVE DETAILS AND A CRITICAL ASSESSMENT OF RECENTLY PUBLISHED DATA ON VARIOUS CHEMICAL FORMS OF ARSENIC, THEIR EXPOSURE, AND IMPLICATIONS ON HUMAN AND ENVIRONMENTAL HEALTH. 2023 5 3591 26 IMPAIRED ONE CARBON METABOLISM AND DNA METHYLATION IN ALCOHOL TOXICITY. EXCESSIVE ALCOHOL CONSUMPTION IS A PROMINENT PROBLEM AND ONE OF THE MAJOR CAUSES OF MORTALITY AND MORBIDITY AROUND THE WORLD. LONG-TERM, HEAVY ALCOHOL CONSUMPTION IS ASSOCIATED WITH A NUMBER OF DELETERIOUS HEALTH CONSEQUENCES, SUCH AS CANCER, HEART AND LIVER DISEASE, A VARIETY OF NEUROLOGICAL, COGNITIVE, AND BEHAVIORAL DEFICITS. ALCOHOL CONSUMPTION IS ALSO ASSOCIATED WITH DEVELOPMENTAL DEFECTS. THE CAUSES OF ALCOHOL-INDUCED TOXICITY ARE PRESENTLY UNCLEAR. ONE OF THE MECHANISMS UNDERLYING ALCOHOL TOXICITY HAS TO DO WITH ITS INTERACTION WITH FOLIC ACID/HOMOCYSTEINE OR ONE-CARBON METABOLISM (OCM). OCM IS A MAJOR DONOR OF METHYL GROUPS FOR METHYLATION, PARTICULARLY DNA METHYLATION CRITICAL FOR EPIGENETIC REGULATION OF GENE EXPRESSION, AND ITS DISTURBANCE MAY COMPROMISE DNA METHYLATION, THEREBY AFFECTING GENE EXPRESSION. OCM DISTURBANCE MEDIATED BY NUTRIENT DEFICITS IS A WELL-KNOWN RISK FACTOR FOR VARIOUS DISORDERS AND DEVELOPMENTAL DEFECTS (E.G., NEURAL TUBE DEFECTS). IN THIS REVIEW, WE SUMMARIZE THE ROLE OF OCM DISTURBANCE AND ASSOCIATED EPIGENETIC ABERRATIONS IN CHRONIC ALCOHOL-INDUCED TOXICITY. IN THIS REVIEW, WE SUMMARIZE THE ROLE OF ONE-CARBON METABOLISM (OCM) ABERRATIONS IN CHRONIC ALCOHOL-INDUCED TOXICITY. OCM IS A MAJOR DONOR OF METHYL GROUPS FOR METHYLATION REACTIONS, PARTICULARLY DNA METHYLATION CRITICAL FOR EPIGENETIC REGULATION OF GENE EXPRESSION. ALCOHOL INTERFERENCE WITH OCM AND CONSEQUENT REDUCED AVAILABILITY OF METHYL GROUPS, IMPROPER DNA METHYLATION, AND ABERRANT GENE EXPRESSION CAN PLAY A CAUSATIVE ROLE IN ALCOHOL TOXICITY. 2014 6 6422 31 THE THIN-FAT PHENOTYPE AND GLOBAL METABOLIC DISEASE RISK. PURPOSE OF REVIEW: THERE HAS BEEN A GREAT DEAL OF INTEREST IN THE THIN-FAT PHENOTYPE EVIDENT IN ASIAN INDIANS AND ITS RISK ASSOCIATIONS IN THE EPIDEMIC OF NONCOMMUNICABLE CHRONIC DISEASE ASSOCIATED WITH IT. THE CAUSE OF THIS PHENOTYPE IS PROBABLY RELATED TO LIFESTYLE AND ENVIRONMENT; HOWEVER, GENOTYPIC AND EPIGENETIC MODIFICATIONS IN UTERO ALSO HAVE BEEN CONSIDERED. RECENT FINDINGS: THE THIN-FAT PHENOTYPE OCCURS WHEN FAT IS ADDED TO AN ALREADY THIN FRAME. THIS MAY OCCUR WITH RURAL-URBAN MIGRATION, WHEN POSITIVE ENERGY BALANCE OCCURS IN A MIGRATING POPULATION WHO WERE PREDOMINANTLY THIN AND PHYSICALLY ACTIVE TO BEGIN WITH. THE ROLE OF THE PRE-EXISTING SKELETAL MUSCLE MASS AND ITS INTERACTION WITH NEWLY DEPOSITED FAT MUST BE CONSIDERED. THE THIN-FAT PHENOTYPE MAY BE PROGRAMMED DURING FETAL GROWTH, BUT THE EVIDENCE FOR THIS PHENOMENON IS STILL NOT COMPLETELY CLEAR. FINALLY, ALTHOUGH THERE IS INCREASED CHRONIC DISEASE MORBIDITY AT LOWER BMI AND YOUNGER AGE IN SOUTH ASIAN POPULATIONS, BMI-RELATED MORTALITY DOES NOT APPEAR TO FOLLOW THIS TREND. SUMMARY: AT PRESENT, THE WEIGHT OF EVIDENCE APPEARS TO LINK THE THIN-FAT PHENOTYPE TO AN ENVIRONMENTAL AND LIFESTYLE PHENOMENON OCCURRING IN PREVIOUSLY THIN PEOPLE. THIS IS PARTICULARLY RELEVANT IN INDIA, GIVEN THE PACE OF TRANSITION OVER THE LAST TWO DECADES. 2011 7 4736 30 NOVEL EPIGENETIC BIOMARKERS MEDIATING BISPHENOL A EXPOSURE AND METABOLIC PHENOTYPES IN FEMALE MICE. THERE IS COMPELLING EVIDENCE THAT EPIGENETIC MODIFICATIONS LINK DEVELOPMENTAL ENVIRONMENTAL INSULTS TO ADULT DISEASE SUSCEPTIBILITY. ANIMAL STUDIES HAVE ASSOCIATED PERINATAL BISPHENOL A (BPA) EXPOSURE TO ALTERED DNA METHYLATION, BUT THESE STUDIES ARE OFTEN LIMITED TO CANDIDATE GENE AND GLOBAL NON-LOCI-SPECIFIC APPROACHES. BY USING AN EPIGENOME-WIDE DISCOVERY PLATFORM, WE ELUCIDATED EPIGENETIC ALTERATIONS IN LIVER TISSUE FROM ADULT MICE OFFSPRING (10 MONTHS) FOLLOWING PERINATAL BPA EXPOSURE AT HUMAN PHYSIOLOGICALLY RELEVANT DOSES (50-NG, 50-MUG, AND 50-MG BPA/KG DIET). BIOLOGICAL PATHWAY ANALYSIS IDENTIFIED AN ENRICHMENT OF SIGNIFICANT DIFFERENTIALLY METHYLATED REGIONS IN METABOLIC PATHWAYS AMONG FEMALES. FURTHERMORE, THROUGH THE USE OF TOP ENRICHED BIOLOGICAL PATHWAYS, 4 CANDIDATE GENES WERE CHOSEN TO ASSESS DNA METHYLATION AS A MEDIATING FACTOR LINKING THE ASSOCIATION OF PERINATAL BPA EXPOSURE TO METABOLIC PHENOTYPES PREVIOUSLY OBSERVED IN FEMALE OFFSPRING. DNA METHYLATION STATUS AT JANUS KINASE-2 (JAK-2), RETINOID X RECEPTOR (RXR), REGULATORY FACTOR X-ASSOCIATED PROTEIN (RFXAP), AND TRANSMEMBRANE PROTEIN 238 (TMEM238) WAS USED WITHIN A MEDIATIONAL REGRESSION ANALYSIS. DNA METHYLATION IN ALL FOUR OF THE CANDIDATE GENES WAS IDENTIFIED AS A MEDIATOR IN THE MECHANISTIC PATHWAY OF DEVELOPMENTAL BPA EXPOSURE AND FEMALE-SPECIFIC ENERGY EXPENDITURE, BODY WEIGHT, AND BODY FAT PHENOTYPES. DATA GENERATED FROM THIS STUDY ARE CRUCIAL FOR DECIPHERING THE MECHANISTIC ROLE OF EPIGENETICS IN THE PATHOGENESIS OF CHRONIC DISEASE AND THE DEVELOPMENT OF EPIGENETIC-BASED PREVENTION AND THERAPEUTIC STRATEGIES FOR COMPLEX HUMAN DISEASE. 2017 8 6594 35 TUMOR-AUGMENTING EFFECTS OF GESTATIONAL ARSENIC EXPOSURE ON F1 AND F2 IN MICE. THE CONSEQUENCES OF EARLY-LIFE EXPOSURE TO CHEMICALS IN THE ENVIRONMENT ARE EMERGING CONCERNS. CHRONIC EXPOSURE TO NATURALLY OCCURRING INORGANIC ARSENIC HAS BEEN KNOWN TO CAUSE VARIOUS ADVERSE HEALTH EFFECTS, INCLUDING CANCERS, IN HUMANS. ON THE OTHER HAND, ANIMAL STUDIES BY DR. M. WAALKES' GROUP REPORTED THAT ARSENITE EXPOSURE OF PREGNANT F0 FEMALES, ONLY FROM GESTATIONAL DAY 8 TO 18, INCREASED HEPATIC TUMORS IN THE F1 (ARSENITE-F1) MALES OF C3H MICE, WHOSE MALES TEND TO DEVELOP SPONTANEOUS HEPATIC TUMORS LATER IN LIFE. SINCE THIS MICE MODEL ILLUMINATED NOVEL UNIDENTIFIED CONSEQUENCES OF ARSENIC EXPOSURE, WE WISHED TO FURTHER INVESTIGATE THE BACKGROUND MECHANISMS. IN THE SAME EXPERIMENTAL MODEL, WE IDENTIFIED A VARIETY OF FACTORS THAT WERE AFFECTED BY GESTATIONAL ARSENIC EXPOSURE, INCLUDING EPIGENETIC AND GENETIC CHANGES, AS POSSIBLE CONSTITUENTS OF MULTIPLE STEPS OF LATE-ONSET HEPATIC TUMOR AUGMENTATION IN ARSENITE-F1 MALES. FURTHERMORE, OUR STUDY DISCOVERED THAT THE F2 MALES BORN TO ARSENITE-F1 MALES DEVELOPED HEPATIC TUMORS AT A SIGNIFICANTLY HIGHER RATE THAN THE CONTROL F2 MALES. THE RESULTS IMPLY THAT THE TUMOR AUGMENTING EFFECT IS INHERITED BY ARSENITE-F2 MALES THROUGH THE SPERM OF ARSENITE-F1. IN THIS ARTICLE, WE SUMMARIZED OUR STUDIES ON THE CONSEQUENCES OF GESTATIONAL ARSENITE EXPOSURE IN F1 AND F2 MICE TO DISCUSS NOVEL ASPECTS OF BIOLOGICAL EFFECTS OF GESTATIONAL ARSENIC EXPOSURE. 2017 9 4602 23 NECESSITY OF EPIGENETIC EPIDEMIOLOGY STUDIES ON THE CARCINOGENESIS OF LUNG CANCER IN NEVER SMOKERS. BASED ON EPIDEMIOLOGICAL AND GENOMIC CHARACTERISTICS, LUNG CANCER IN NEVER SMOKERS (LCNS) IS A DIFFERENT DISEASE FROM LUNG CANCER IN SMOKERS. BASED ON CURRENT RESEARCH, THE MAIN RISK FACTOR FOR LCNS MAY BE AIR POLLUTION. A RECENT CASE-CONTROL STUDY IN KOREANS REPORTED THAT NITROGEN DIOXIDE (NO2) MAY BE A RISK FACTOR FOR LCNS. ADDITIONALLY, A COHORT STUDY SHOWED THAT EXPOSURE TO NO2 WAS ASSOCIATED WITH SIGNIFICANT HYPOMETHYLATION. THUS, EPIGENETIC EPIDEMIOLOGY STUDIES ARE NEEDED IN THE NEAR FUTURE TO EVALUATE THE CARCINOGENESIS OF LCNS ACCORDING TO CHRONIC EXPOSURE TO AIR POLLUTION AND/OR VIRAL INFECTIONS. 2018 10 4019 36 LOW-DOSE OR LOW-DOSE-RATE IONIZING RADIATION-INDUCED BIOEFFECTS IN ANIMAL MODELS. ANIMAL EXPERIMENTAL STUDIES INDICATE THAT ACUTE OR CHRONIC LOW-DOSE IONIZING RADIATION (LDIR) (