饮水中微囊藻毒素与我国原发性肝癌关系的研究

目的：阐明在肝癌高发区东南沿海肝癌与水中微囊藻毒素（MC）的关系。方法应用生态学、病例对照、定群、Meta分析和危险度评估等流行病学调查方法，通过F344和HBVx转基因鼠动物试验进一步证明。结果：用Meta分析的方法对6个肝癌病例进行对照研究，结果研究，饮沟塘水的合并比数比为2．46（95％CI，1．69－2．59），归因危险度为30．39％（95％CI，23．30％－34．47％）一致性检验P＞0．05。沟塘水由于富营养化，造成藻类疯长，藻细胞死后释出藻类毒素。实验室研究证明，这种毒素是趋肝的促癌因素，在HBVx转基因鼠中，与起始剂黄曲霉素素和MC一起可引起肝细胞肝癌。结论沟塘水中以MC为代表的藻类毒素是趋肝致肝炎和肝癌的促癌剂。MC与乙型肝炎和黄典霉素素3个环境危险因素组合，可能是我国肝癌高发的原因之一。

The relationship cyanotoxin(Microcystin,MC)in pond-ditch water and primary liver cancer in China

OBJECTIVE: To explore the relationship between primary liver cancer (PLC) and MC in drinking pond-ditch water. METHODS: Epidemiological and ecological assays, Meta-analysis and risk assessment were used in this study. Cyanotoxin (Microcystin, MC) in the water of different sources was detected by ELISA. The F344 and HBVx transgenic mice were used to confirm the promotion effect on PLC and the synthetically carcinogenic effect of HBV, aflatoxin and MC. RESULTS: Using Meta-analysis the results of six case-control studies showed that the pooled odds ratio (OR) was 2.46 (95% CI 1.69-2.59), population attributable rick (PAR) was 30.39% (95% CI, 23.30%-37.47%), heterogeneity test P > 0.05. Eutrophication led to cyanobacterial bloom in the pond-ditch water. Cyanotoxin released from dead cyanobacteria was hepatotactic tumor promoter. In HBVx transgenic rats, hepatocellular carcinoma was induced by the joint administration of aflatoxin B1 and cyanotoxin. Epidemiological study showed that the recombined index of HBsAg, aflatoxin-albumin adducts and drinking of pond-ditch water correlated with PLC mortalities in 13 townships. CONCLUSION: Microcystin in the pond-ditch water is a hepatotactic toxin which can induce hepatitis and promote development of hepatocellular carcinoma. The combined effect of microcystin, HBV and aflatoxin may be responsible for the endemicity of PLC.