Hilf R, Murant R S, Narayanan U, Gibson S L
Cancer Res. 1986 Jan;46(1):211-7.
The effects of hematoporphyrin derivative-induced photosensitization on the levels of adenosine triphosphate (ATP) in R3230AC mammary adenocarcinomas were studied. Enzymatically dissociated tumor cells were exposed to various doses of hematoporphyrin derivative (HPD) in vitro plus photoradiation. A drug and light dose-dependent decrease in cellular ATP levels was observed; ATP levels were reduced by 60% after treatment with 7.0 micrograms HPD per ml plus 0.72 J total energy density per cm2. Cell viability, assessed by exclusion of trypan blue, displayed an apparently coordinate behavior to ATP levels. The effects of hematoporphyrin derivative plus photoradiation were examined in the presence of oligomycin, an inhibitor of mitochondrial oxidative phosphorylation, or iodoacetate, an inhibitor of glycolysis, experiments designed to elucidate the site of action leading to reduced ATP levels. The results indicated that HPD-induced photosensitization had little additive effects to oligomycin-sensitive ATP production, whereas significant further reduction in ATP levels was obtained by HPD-induced photosensitization in the presence of iodoacetate. Taken together, along with earlier studies of selected mitochondrial enzymes, we conclude that HPD plus photoradiation inhibits mitochondrial function leading to reduction in cellular ATP levels and loss of viability.
研究了血卟啉衍生物诱导的光敏感作用对R3230AC乳腺腺癌中三磷酸腺苷（ATP）水平的影响。将酶解后的肿瘤细胞在体外暴露于不同剂量的血卟啉衍生物（HPD）并进行光辐射。观察到细胞ATP水平呈药物和光剂量依赖性下降；每毫升7.0微克HPD加每平方厘米0.72焦耳总能量密度处理后，ATP水平降低了60%。通过台盼蓝排斥法评估的细胞活力与ATP水平表现出明显的协同变化。在存在线粒体氧化磷酸化抑制剂寡霉素或糖酵解抑制剂碘乙酸的情况下，研究了血卟啉衍生物加光辐射的作用，这些实验旨在阐明导致ATP水平降低的作用位点。结果表明，HPD诱导的光敏感作用对寡霉素敏感的ATP生成几乎没有累加效应，而在碘乙酸存在的情况下，HPD诱导的光敏感作用会使ATP水平进一步显著降低。综合这些结果以及早期对特定线粒体酶的研究，我们得出结论，HPD加光辐射会抑制线粒体功能，导致细胞ATP水平降低和活力丧失。
