Disruption of normal cellular bioenergetics in Balb/c mice by mitomycin C

Mitomycin C (MMC) is an antineoplastic agent with activity against a wide variety of tumours. The primary cellular target for MMC's antineoplastic activity is thought to be nuclear DNA. The interactions of MMC with nuclear DNA have been studied extensively. This laboratory has shown 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 whether 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 MMC treatment, heart, liver and kidney tissues were excised and tissue ATP levels were assessed. Heart tissue was the most sensitive to the MMC treatment and significant decreases in ATP levels were observed at all MMC dosages tested. Liver and kidney tissues showed significant decreases only at the highest dosages tested. These studies demonstrate that tissue specific disruption of cellular bioenergetics occurs following MMC exposure resulting in a decrease of tissue ATP levels.