DISRUPTION OF NORMAL CELLULAR BIOENERGETICS IN BALB C MICE BY MITOMYCIN-C/

Mitomycin C (MMC) is an antineoplastic agent with activity against a w ide variety of tumours. The primary cellular target for MMC's antineop lastic activity is thought to be nuclear DNA. The interactions of MMC with nuclear DNA have been studied extensively. This laboratory has sh own recently that MMC also interacts with mitochondrial DNA, resulting in a conformational change from the supercoiled to the relaxed state. This interaction could cause mitochondrial dysfunction, resulting in a loss of cellular ATP. The present studies were designed to test whet her treatment with MMC would affect tissue ATP levels in Balb/c mice. Mice were treated with single, or multiple (2) i.p. injections of 0, 5 , 10 or 20 mg MMC kg(-1) body wt. Forty-eight hours after the final MM C treatment, heart, liver and kidney tissues were excised and tissue A TP levels were assessed. Heart tissue was the most sensitive to the MM C treatment and significant decreases in ATP levels were observed at a ll MMC dosages tested. Liver and kidney tissues showed significant dec reases only at the highest dosages tested. These studies demonstrate t hat tissue specific disruption of cellular bioenergetics occurs follow ing MMC exposure resulting in a decrease of tissue ATP levels.