Microcystins (cyanobacterial toxins) in drinking water enhance the growth of aberrant crypt foci in the mouse colon

Microcystis aeruginosa produces toxic cyclic peptides called microcystins, potent hepatotoxins that have been implicated in tumor promotion in skin an d liver. The model used in this investigation was the azoxymethane (AOM)-in duced aberrant crypt focus (ACF) in the male C57Bl/6J mouse colon. Three in traperitoneal (ip) injections of 5 mg/kg AOM were administered at 7-d inter vals to mice; 19 d after the last AOM injection, drinking water containing Microcystis extract was commenced and continued for a further 212 d. The co ntent of microcystins in the drinking water was determined by mouse bioassa y, high-performance liquid chromatography ( HPLC), capillary electrophoresi s, and protein phosphatase inhibition. The doses employed were 0, 382, and 693 mu g/kg bodyweight/d at the midpoint of the trial. Following postmortem examination blood cells, serum enzymes and organ pathology were investigat ed. A significant microcystin dose-dependent increase in the area of aberra nt crypt foci was observed. There was no marked increase in the number of c rypts/colon. Two overt colonic tumors (similar to 30 mm(3)) were seen in mi crocystin-treated mice, and one microscopic colonic tumor in an AOM-alone-t reated mouse. This investigation provides the first evidence for the stimul ation of preneoplastic colon tumor growth by microcystin.