The Role Of Oxidative Damage Induced By Environmental Chemicals In Environmental Carcinogenesis

Objective The study aims to explore the potential mechanism of DNA oxidative damage induced by exposed environmental chemicals in carcinogenesis. We select Shenqiu county; Henan province that located in Huai River region as the study area. Based on case-control study, we develop a ultrasensitive UPLC-TQD (UPLC-MS-MS) method for the analysis of benzo(a)pyrene(B(a)P), benzo(g,h,i)perylene(B(g,h,i)P), dibenzo(a,h)anthrancene(DB(a,h)A) in plasma and 2-naphthol(2-OHN),2-hydroxyfluorene(2-OHF), 1-hydroxypyrene(1-OHP) in urine for evaluation of exposed level of the region; and levels of malondialdyde (MDA) in plasma and urine was used to be for assessment of lipid peroxidation, and level of urinary etheno-dC adduct as a biomarker was used for assessment of oxidative DNA damage. The results of study will be helpful to explore the potiential mechanism of oxidative damage induced by environmetal chemicals in carcinogenesis by comparison of those biomarkers between in high cluster and low cluster area and comparison between case and control.Methods Based on a population-based case-control study, we enroll cancer cases of esophageal cancer, gastric cancer and liver cancer and controls, the biospecimens for each participate including blood and urine were collected. A sensitive solid phase extraction-UPLC/MS/MS method was developed to measure levels of benzo(a)pyrene, benzo(g,h,i)perylene, dibenzo(a,h)anthracene in plasma, and levels of urinary 2-naphthol, 2-hydroxy-fluorene and 1-hydroxy-pyrene. An ultrasensitive DNPH derivative-HPLC-UV was used to determine MDA metabolite in blood and urine; a stable isotope dilution ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry was developed to analyse urinary excertion of etheno-dC. SPSS 17.0 was used for data statistic analysis.Results 1 Main results of PAHs:Urinary 1-hydroxypyrene in 66.9% of all subjects was higher than recommended BEL (biological exposure limit,0.11μmol/molCr) of common population, the result indicate that high exposure of PAHs in research area; No significant differences of PAHs levels in plasma and urine were found between high cluster and low cluster areas; Levels of B(a)P, B(g,h,i)P were significantly higher in cases than that in controls; Urinary 2-OHF,1-OHP levels were significantly lower in cases than that in controls; Level of plasma B(g,h,i)P in esophageal cancer group was significantly higher than that in control; Urinary 1-OHP level was significantly lower than that in control; Plasma B(a)P, B(g,h,i)P levels in gastic and liver cancer cases were significantly higher than that in controls, Urinary 2-OH-F was significantly lower than that in controls.2 Main results of oxidative damage:No significant difference of plasma and urinary MDA metabolite was found between high cluster and low cluster area; Plasma and urinary MDA metabolites were significantly higher in cancer patients than that in controls, espesically in esophageal and gastric cancer cases; Urinary excretion of etheno-dC in high cluster was significantly higher than that in low cluster area, level of urinary etheno-dC was shown high trend in cancer cases compared with controls, but no significantly difference was found.Conclusion:The results of the study indicate that exposed level of PAHs is high in selected research area, however, PAHs is not a leading chemical pollutants in selected research area. Exposure of PAHs may be a risk factor linked with incidence of esophageal, gastric and liver cancers. Oxidative DNA damage induced by oxidative stress/lipid peroxidation is shown high level in cancer cases, the results indicate that level of oxidative DNA damage in cancer cases is high than that in contros. Oxidative DNA damage deriving from environmetal chemicals exposure may be one of potiential mechanism of carcinogenesis, and biomarkers of oxidative DNA damage could be used in cancer risk assessment in areas with environment pollution.