Health Harm And Genotoxicity Study Of Individuals Exposed Occupationally To Arsenic

Arsenic is a familiar environmental toxicoid that affects our health, and it isaffirmed that arsenic can induce cancer on human being. It was reported thatarsenic could induce skin damage, tendon hyporeflexia, liver function damage,cardivascular and neuropathy system pathological changes by both animalexperiment and epidemiology survey. In addition, arsenic exposure wasassociated with skin cancer, urinary bladder cancer, lung cancer, stomach cancer,liver cancer, prostate cancer and rectum cancer. But genotoxicity and carcinogeni-city mechanism is not clear, and a long way is needed to go. It may be greatreason that ideal animal model can not been established, and the interferentialfactors of exposure evaluation on epidemiology can not been strictly controlled.This will harm people health greatly, and it is of great difficult to study themechanism how arsenic induce damage to human beng.Since different arsenic compounds in bodies were mensurated respectivelyby Braman, the study on metabolism of arsenic developes quickly. There aremore and more researches sustain that monomethylarsonous acid (MMA) anddimethylarsinous acid (DMA) are more toxic than inorganic arsenic. At the sametime, MMA and DMA may play key role in inducing genotoxicity andcarcinogenesis. It is not consistent with the previous ubiquitous idea thatinorganic arsenic was more toxic than organic arsenic. The process of metabolismof arsenic, and/or metabolites came from it in human being may inducegenotoxicity and carcinogenesis, which will be a important aim that need further arsenic in animals and human beings may be one of the reason why ideal animalmodel on genotoxicity and carcinogenesis of arsenic could not been established.So epidemiology is great important for us to further understand the toxicmechanism of arsenic. But only when interferential factors are controlled strictly,valuable results could be gained.The research field we chose is a special mill that produces arsenic in YunNan province. The main factor that affect worker's health is arsenic compounds.It is in favor of the research on occupational health hazard, dose-effectrelationship, and also offer a good chance to resolve the problem of extrapolatebetween different species and doses, which is very difficult to most investigation.In this study, we chose an arsenic mill in YunNan province as investigationfield, and search the primary factors that affect workers' health by engineeringanalysis and occupational health investigation for arsenic exposure, and studyoccupational harm actuality by occupational health ward examination andestimation of quality of life. Then, the DNA and chromosome damage in workersexposed to arsenic were investigated, and gene-specific damage was measuredquantificationally. Forepart effect biomarkers for arsenic exposure were explored,and the mechanism on genotoxicity and carcinogenesis of arsenic were studieddeeply.PartⅠEngineering analyse and occupational health investigation of arsenic mill in YunNan provinceIt is a special mill for arsenic trioxide and metal arsenic production. Arsenictrioxide was produced by reverberator smelting, and materials are arsenic trioxidewhich purity is over 94%, and charcoal as reducing agent to produce metalarsenic. The primary occupational harm and possible influence factors werestudied by material balance calculation, production technics flow analyse andoccupational health investigation.In this investigation, many means were used to investigate occupationalharms including going into arsenic producing workshop, looking in production technics flow and main equipments, and analyzing the sort, distribution andextent of main occupational harm factors caming from production process, andoccupational defend measures. The components and contents of former andsupplement materials, arsenic trioxide, metal arsenic, smelting residues andexhaust gas were measured to calculate material balance of arsenic, iron, sulfur,carbon and so on, and understand their source and whither. The results comingfrom occupational health investigation show that pollution of arsenic compoundwas severe in workshop, and this is the primary reason that harmful to workers,especially in genotoxicity and carcinogenesis, and there were few interferentialfactors.PartⅡThe occupational health examination and quality life evaluation of workers exposed to arsenicIn this study, all objects were examined by uniform table and one meansaccording to the administrant ways of occupational health ward, nationaloccupational diagnosis standard strictly, and organic and inorganic urinary arsenicwere measured. At the same time, the quality life of all objects were selfexamined using quality life scale SF-36 recommended by WHO.Results coming from physical examination showed that the incidence rate ofskin damage, tendon hyporeflexia, cardivascular system pathological changeswere high in workers, but low in the others. Total urinary arsenic in allindividuals exposed occupationally to arsenic was more than 35ug/L, which is theBiological Exposure Indices (BEIs) on total urinary arsenic constituted up to dateand recommended by American Conference of Government Industrial Hygienists(ACGI). The concentrations of total urinary arsenic in high exposure workerswere as over 10 times as the the data's, and organoic and inorganic urinaryarsenic of individuals exposed occupationally to arsenic were all very high.Results of quality life evaluation of individuals exposed to arsenic showedthat scores on physical function were higher, but that on Pain, General health,Vitality, Role-emotional, Mental Health were lower than references' (P＜0.05). Vitality, Role-emotional, Mental Health were lower than references' (P＜0.05)It could be thought that individuals exposed occupationally to arsenic were ininferior health partly.PartⅢDNA damage measure of individuals exposed occupationally to arsenicIt is easy operation, not needing especial instrument, holding highsensitivity, and is good for epidemiology to measure urinary 8-OHdG by ELISAmethod, and to detect DNA damage of lymphocyte in peripheral blood by ouncewhole blood comet assay. Those assays were used to measure DNA damage ofindividuals exposed occupationally to arsenic.Results showed that high exposure individuals hold more urinary 8-OHdGthan references' (P＜0.05) in male, and the contents in male workers were lowerthan that in females in low exposure (P＜0.05). The increascd tendencies ofurinary 8-OHdG levels with the organic arsenic concentration were found inworkers (spearman'correlation coefficient, r_s=0.279, P=0.019). The comet rateand tail lengthof of lymphocyte of workors were all higher than references' (P＜0.01).PartⅣGene-specific damage and arsenic metabolism in individuals exposed occupationally to arsenicThe theory to measure quantificationally gene-specific damage usingreal-time quantitative PCR is that DNA damage of alive cell will disturb Tappolymerization enzyme, which results in needing more reaction circles in PCR toreach one output (this means Ct value of PCR enlarging), and damage indexs ofcertain segment of specific gene increasing (this means expanding efficiency ofPCR decreasing). The assay to measure quantificationally the damage to exon 5and 8 of p53 gene of lymphocyte in peripheral blood using real-time quantitativePCR were established, and used to molecular epidemiology for individualsexposed occupationally to arsenic. The damage index of high exposure individuals were higher than references' (P＜0.05). The increased tendencies of damage indexs of exon 5 of p53 gene withthe logarithm value of organic arsenic concentration was found in objects usingboth pearson correlation (pearson' correlation coefficient=0.351, P=0.012)and stepwise linear regression analyzing (Standardized coefficient=0.648, P=0.018).PartⅤChromosome damage measure of individuals exposedoccupationally to arsenicMicronucleus rates of lymphocyte coming from peripheral blood inindividuals exposed occupationally to arsenic were measured by routine cultureassay. Vein blood of all objects were adopted and cultured on the spot, andperformed routine culture assay immediately.Results show that both micronucleated cell and micronucleus frequency oflymphocyte were higher than references' (P＜0.01). The increased tendencies ofmicronucleied cells and micronucleus frequency with the product of organicarsenic concentration and service length were found in workers (r_s=0.356, P=0.024. r_s=0.347, P=0.028). Chromosome damage in individuals exposedoccupationally to arsenic for a long time were induced, and the increasedtendencies of chromosome damage with the accumulation of metabolism inarsenic were found. The cytogenetic induced by the metabolism of inorganicarsenic were one route of the carcinogenesis of arsenic in human for a long time.