Hodgkiss R J, Stratford M R, Watfa R R
Gray Laboratory of the Cancer Research Campaign, Mount Vernon Hospital, Northwood, Middlesex, England.
Int J Radiat Oncol Biol Phys. 1989 May;16(5):1297-300. doi: 10.1016/0360-3016(89)90302-7.
The effect of hypoxic cell radiosensitizers is increased when mammalian cells are depleted of endogenous glutathione by buthionine sulphoximine pre-treatment in vitro; a similar gain has not been observed in tumors in vivo despite evidence of glutathione depletion in vivo following buthionine sulphoximine treatment. However, concentrations of biological reducing agents other than glutathione were not measured in the in vivo experiments. Other reducing agents found in tumors include alpha-tocopherol, which reduces the sensitizing efficiency of nitro-aromatic sensitizers in thiol-depleted mammalian cells. These data suggest that the failure to observe large gains in misonidazole sensitizing efficiency in thiol-depleted tumors in vivo may be due, in part, to the presence of biological reducing agents such as alpha-tocopherol.
当在体外通过丁硫氨酸亚砜亚胺预处理使哺乳动物细胞内源性谷胱甘肽耗竭时,乏氧细胞放射增敏剂的效果会增强;尽管有证据表明丁硫氨酸亚砜亚胺治疗后体内谷胱甘肽会耗竭,但在体内肿瘤中并未观察到类似的效果增强。然而,在体内实验中并未测量除谷胱甘肽之外的生物还原剂的浓度。肿瘤中发现的其他还原剂包括α-生育酚,它会降低硝基芳香族增敏剂在巯基耗竭的哺乳动物细胞中的增敏效率。这些数据表明,在体内巯基耗竭的肿瘤中未观察到米索硝唑增敏效率大幅提高,部分原因可能是存在诸如α-生育酚等生物还原剂。