Abstracts:

ENHANCEMENT OF THE GROWTH OF MURINE COLON CANCER PRECURSORS BY MICROCYSTIN-CONTAMINATED DRINKING WATER

Andrew R. Humpage, Stephen J. Hardy, Emma J. Moore, Suzanne M. Froscio and Ian R. Falconer.

Department of Clinical and Experimental Pharmacology, and the Cooperative Research Centre for Water Quality and Treatment, University of Adelaide, South Australia, 5005.


Microcystis aeruginosa is a common cyanobacterium which produces toxic cyclic peptides called microcystins, potent hepatotoxins that have been implicated in tumour promotion in skin and liver. Cyanobacteria grow in many drinking water sources, so there is the potential for exposure of human water consumers. We have performed a series of studies to assess the potential for tumour promotion and carcinogenesis in mankind by cyanobacterial toxins such as the microcystins. In the present investigation, the model used was the azoxymethane (AOM)-induced aberrant crypt foci in the male C57BL/6J mouse colon. Tumours were initiated in the colons of mice by repeated AOM treatment and then drinking water containing Microcystis extract was supplied and continued for 212 days. The content of microcystins in the drinking water was determined by mouse bioassay, High Performance Liquid Chromatography (HPLC), capillary electrophoresis and protein phosphatase inhibition. The doses employed were approximately 0, 400 and 700 ug microcystin-LR equivalent/kg bodyweight/day. Although growth was initially reduced in the AOM dosed mice, no significant long-term effect of microcystin on growth rate was seen. At the end of the exposure period, a detailed post-mortem examination was performed followed by investigation of effects on haematology, serum chemistry and organ histopathology. A microcystin dose-dependant decrease in albumin concentration and increase in alkaline phosphatase activity in sera indicated sub-lethal toxicity. Measurement of aberrant crypt foci showed a significant (p less than 0.005) microcystin dose-dependant increase in both median and mean focus area. This investigation has provided the first evidence of stimulation of preneoplastic colon tumours by microcystin.

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