藻类毒素与饮水氯化消毒副产物致癌作用的实验研究

Conventional surface water treatment processes are not effective enough to remove all cyanobacterial toxins, and chronic exposure of cyanobacterial toxins in drink water may be a cause of tumour-promotion effect. Certain disinfections by-products (DBPs) in drinking water are found to be mutagenic. Coexistence of DBPs and cyanobacterial toxins in drinking water may lead to potential synergistic effects during carcinogenesis.OBJECTS: The goal of this study is to investigate the potential synergistic effects between DBPs and cyanobacterial toxins during carcinogenesis, and explore its potential mechanism.METHODS: Mutagenicity screening tests including Ames test, Micronuclei and UDS were used to evaluate the mutagenicities of DBPs, and the effects of cyanobacterial toxins on cell cycle and related gene expression were investigated in vitro. A two-stage hepatocarcinogenesis rat model (Solt-Farber Model) was established with DBPs and cyanobacterial toxins applied as initiator and promoter, respectively. The histopathological changes in liver were observed, and expressions of TCF/ELK-1, c-fos, c-jun and GSTPi were detected by means of immunohistochemical staining, Western-blot, RT-PCR and ISH. DNA binding activities of AP-1 was analyzed by EMSA as well. The relationship among the expression of TCF/ELK-1, c-fos, c-jun, and GSTPi were also under onsideration..RESULTS: The results showed that DBPs were mutagenic, and cyanobacterial toxins could up-regulate the expression of c-fos and c-jun in vitro. The results also indicated that hyperplastic and precancerous foci as well as nodule were induced in livers of rats treated with DBPs and cyanobacterial toxins, and up-regulated expressions of ELK-1,c-jun,c-fos and DNA binding activity of AP-1 were all seen in hepatocyte of rats treated with cyanobacterial toxins. DBPs alone could induce expressions of GSTPi mRNA and protein in livers. Compared to DBPs, cyanobacterial toxins alone couldn't induce the changes of corresponding GSTPi, but can promote the expressions of GSTPi mRNA and protein induced by DBPs. CONCLUSIONS: The results suggest that DBPs have potential tumour-initiating activities while cyanobacterial toxins have potential tumour-promoting activities. Coexistence of DBPs and cyanobacterial toxins in drinking water may cause potential synergistic effects during carcinogenesis. Inhibitions of protein phosphatase activity and up-regulation of MAPKs signaling pathways thus to promote cell proliferation and malignant transformation initiated by DBPs may be potential tumour promotion mechanism of cyanobacterial toxins coexisting with DBPs in drinking water during carcinogenesis.

水中有毒藻类毒素和消毒副产物共存是当今存在的实际问题。前者具有促癌作用，后者某些是致癌物或致突变物。本研究从水中提取分离纯化藻毒素和氯化副产物经AMESUDSSHE等实验筛选，并研究二者联合作用继而通过动物长期毒理学实验研究氯化消毒副产物和有毒藻类毒素共存时的致癌效应。为藻类毒素卫生标准制定和饮水消毒方法改进提供依据。..