Pritsos C A, Briggs L A
Department of Nutrition, University of Nevada, Reno, USA 89557-0132, USA.
Br J Cancer Suppl. 1996 Jul;27:S15-8.
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.
丝裂霉素C（MMC）是一种抗肿瘤药物，对多种肿瘤具有活性。MMC抗肿瘤活性的主要细胞靶点被认为是核DNA。MMC与核DNA的相互作用已得到广泛研究。本实验室最近表明，MMC还与线粒体DNA相互作用，导致其构象从超螺旋状态转变为松弛状态。这种相互作用可能导致线粒体功能障碍，从而导致细胞ATP的丧失。本研究旨在测试MMC治疗是否会影响Balb/c小鼠的组织ATP水平。小鼠接受单次或多次（2次）腹腔注射0、5、10或20mg MMC/kg体重。在最后一次MMC治疗后48小时，切除心脏、肝脏和肾脏组织并评估组织ATP水平。心脏组织对MMC治疗最为敏感，在所有测试的MMC剂量下均观察到ATP水平显著下降。肝脏和肾脏组织仅在测试的最高剂量下显示出显著下降。这些研究表明，MMC暴露后会发生组织特异性的细胞生物能量学破坏，导致组织ATP水平降低。
