Pritsos C A, Briggs L A, Gustafson D L
Department of Nutrition, University of Nevada, Reno 89557, USA.
Oncol Res. 1997;9(6-7):333-7.
Mitomycin C (MMC) is an anticancer, antibiotic that is currently used clinically against a wide variety of tumors. Nuclear DNA is regarded as the primary cellular target for mitomycin's toxicity. In this study, the effect of MMC on mitochondrial DNA was tested both in vitro and in vivo. EMT6 mouse mammary carcinoma cells were treated with MMC and conformational 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 assayed for mitochondrial integrity. Mitochondrial integrity was lowered in the MMC-treated animals. Liver tissue adenosine triphosphate (ATP) levels were also shown to be significantly decreased in these same animals. We also show that MMC can be activated by mitochondria. These studies provide strong evidence that mitochondrial DNA is a target for MMC and that this interaction has a biochemical consequence that could prove toxic.
丝裂霉素C（MMC）是一种抗癌抗生素，目前临床上用于治疗多种肿瘤。核DNA被认为是丝裂霉素毒性的主要细胞靶点。在本研究中，对MMC在线粒体DNA上的作用进行了体内和体外测试。用MMC处理EMT6小鼠乳腺癌细胞，并测定其线粒体DNA的构象变化，以此作为线粒体DNA损伤的指标。观察到MMC处理剂量与线粒体DNA损伤之间存在剂量依赖关系。对用MMC处理的Balb/c小鼠的肝组织线粒体进行线粒体完整性检测。经MMC处理的动物线粒体完整性降低。这些动物的肝组织三磷酸腺苷（ATP）水平也显著降低。我们还表明MMC可被线粒体激活。这些研究提供了有力证据，证明线粒体DNA是MMC的一个靶点，并且这种相互作用具有可能产生毒性的生化后果。
