Study On Genotoxicity Induced By Chlorinated Acetic Acids Of Disinfection By-products

People pay much attention to the potential carcinogenic harm of chloridized disinfection by-products(DBPs) in drinking water. Up to now, there are more than 200 DBPs have been detected. Zhang Xiaojian estimated that haloacetic acids in chloridized DBPs played a major part in the total carcinogenic risk, beyond 90%. U. S. EPA' s long carcinogenic test reported that dichloroacetic acid(DCA) could induce hepatic cancer in rat and mice, and trichloroacetic acid (TCA) could induce hepatic cancer in mice. But carcinogenic mechanism of chloridized DBPs is still not clear. At the same time, DCA and TCA cannot be confirmed as genotoxic carcinogen based on available results of toxicological test.We used three methods, including Ames assay, comet assay in vitro and in vivo and RDPCR assay, which was established by our laboratory, to study the genotoxicity of DCA and TCA on cell level and molecule level respectively, and to probe into their carcinogenic mechanism.Study on mutagenicity of DCA and TCAIn Ames assay, we used TA97, TA98, TA100 and TA102 as bacterial strain. Different material was used as positive control according to different bacteria. Negative control group was obtained when no positive material and DCA or TCA were added. The result was negative which showed that no mutagenicity was detected out of the test material in different concentration, even when the concentration reached the level of cytotoxicity.Part 2Study on DNA strand-breaking effect of DCA and TCAIn this part, we used V79 cells and hepatocyte of mice to detect whether DCA and TCA could damage DNA of cells in vitro and in vivo. We contrast the effect of once and several times treating in vivo. The results of DCA and TCA werepositive in V79 cell and hepatocyte of mice in vitro and in vivo. Damage aggravated with dosage and treating times increasing.Part 3 Study on p53 gene damage action of DCA and TCAWe used RDPCR established by our laboratory to detect whether DCA and TCA could damage exon7 of p53 gene in rat. The result was that DCA can damage p53 gene in vitro and in vivo, and had two DNA lesion cites. TCA could damage p53genein vitro, and didn' t detect out of positive in vivo. It could be deduced that DCA perhaps expresses its carcinogenicity by damaging p53 gene, and it belongs to genotoxic carcinogen.This research indicated that DCA and TCA belong to genotoxic carcinogen. The mechanism of DCA inducing hepatic cancer in rat is perhaps to damage p53 gene.