A NEW CELLULAR TARGET FOR MITOMYCIN-C - A CASE FOR MITOCHONDRIAL-DNA

Mitomycin C (MMC) is an anticancer, antibiotic that is currently used clinically against a wide variety of tumors. Nuclear DNA is regarded a s the primary cellular target for mitomycin's toxicity. In this study, the effect of MMC on mitochondrial DNA was tested both in vitro and i n vivo. EMT6 mouse mammary carcinoma cells were treated with MMC and c onformational changes in their mitochondrial DNA were determined as a measure of mitochondrial DNA damage. A dose-dependent relationship was observed between MMC treatment dosages and mitochondrial DNA damage. Liver tissue mitochondria from Balb/c mice treated with MMC were assay ed for mitochondrial integrity. Mitochondrial integrity was lowered in the MMC-treated animals. Liver tissue adenosine triphosphate (ATP) le vels were also shown to be significantly decreased in these same anima ls. We also show that MMC can be activated by mitochondria. These stud ies provide strong evidence that mitochondrial DNA is a target for MMC and that this interaction has a biochemical consequence that could pr ove toxic.