Tumour promotion by cyanobacterial toxins.

Abstract

A study of chronic toxicity due to Microcystis in drinking water led to the initial experimental evidence of skin tumour promotion by microcystins. Because the main target for this toxicity is the liver, the later demonstration of accelerated growth of enzymically altered foci of potential hepatocellular carcinoma cells by microcystin was important. The identification of the mechanism of toxic action through inhibition of specific protein phosphatases linked the tumour promotion activity of microcystins to that of okadaic acid. Both inhibit the same enzymes, and both are tumour promoters. The mechanism of this promotion is under active investigation in several laboratories and appears to be related to the role of phosphorylated proteins at key points in cell-cycle control. The relevance of these cellular and sub-cellular mechanisms to human health is being investigated by two independent methods: whole animal exposure studies and epidemiological investigation. The results of a study of chronic microcystin exposure on duodenal and lymphoid tumour growth in mice are reported. Epidemiological work is in progress in Australia and in China. In Australia, where primary hepatocellular carcinoma is rare, a broad survey of cancer mortality and Microcystis contamination of water supplies is underway. In areas of South-Eastern China annual mortality rates for hepatocellular carcinoma are > 60 per 100 000, and these rates of incidence show a strong positive correlation with surface water consumption. Analysis for microcystin in these waters showed concentrations averaging 6.5 μg I-1 compared to no detectable concentration in all but one sample of well water. It is apparent that further investigation of tumour promotion by microcystins is warranted, at molecular, whole animal and epidemiological levels.