Endogenous DNA Adducts Method Establishment And Human Biomonitoring

DNA adducts are an important class of biomarkers.DNA adducts either as acontact (exposure) biomarkers accurately reflect the exposure dose of chemicalpoison to evaluate the toxicity of chemical poisons, biological monitoring andanalysis of exposure to carcinogenic chemical contaminants to provide effectivemeans for the population, but also as effector markers, screening high-risk groups,provide impor-tant information for cancer risk assessment of the organism, the sametime, can be used for the development of rational strategies for cancer prevention andtreatment. the vast majority of mutations in human tissues, can be determinedto beendo-genous.Endogenous DNA damage occurs more frequently than exogenous.So itis the focus of toxicology research to test DNA adductsand has important applicationvalue.However, the levels of endogenous DNA adducts in the body are very low,which requires the sensitivity of our detection method to be high and limits ofdetection to be low and better specificity.Long-term exposure to benzene-induced aplastic anemia and leukemia causalrelationship has been proven by epidemiological studies.UsingCross-sectionalresearchmethod, through the analysis ofbiomarkers inhumanbiological samples (urine, blood), which is related to DNA oxidative damage andantioxidant which is caused bythe final product of benzene metabolites (reactiveoxygen species)-induced oxidative response and lipid peroxidation,we research theassociation between oxidative DNA damage and antioxidant defense mechanismswhich is caused by the"second hit" of Benzene-induced oxidative stress and lipidperoxidation,to reveal carcinogenic benzene poisoning and new molecularmechanisms,which will provide a theoretical basis for the carcinogenic benzenepoisoning and early clinical diagnosis and treatment.The main contents of this paper includes the following two aspects:On the basis of our laboratory study,we establish and optimize an UPLC-ESI-MS/MS method which can detects etheno-DNA adducts (εdA, εdC) inhuman blood.This method have a higher sensitivity,lower LOD,good recovery andneed small samples(about20μg).This method can be applied to quantifyetheno-DNA adducts (εdA, εdC) in large human blood samples. The detection limitsof εdA and εdC are1.45fmol and1.27fmol.2.Using our laboratory detectiong method,we detectedetheno-DNA (εdA, εdC)adducts in the urine and blood samples from factory workers which are exposed tobenzene and non-exposed to benzene,followed by system analysis,usingCross-sectionalresearchmethod,we research the association between oxidative DNAdamage and antioxidant defense mechanisms which is caused by the"second hit" ofBenzene-induced oxidative stress and lipid peroxidation,to reveal carcinogenicbenzene poisoning and new molecular mechanisms,which will provide a theoreticalbasis for the carcinogenic benzene poisoning and early clinical diagnosis andtreatment.