Mulcahy R T
Int J Radiat Oncol Biol Phys. 1986 Aug;12(8):1393-5. doi: 10.1016/0360-3016(86)90179-3.
Experiments were designed to determine whether carbamoylation-related inhibition of glutathione reductase (GR) was involved in the previously reported correlation between nitrosourea carbamoylating activity (defined by the extent of binding to L-lysine) and the magnitude of Misonidazole (MISO) chemopotentiation. The extent to which 12 different nitrosoureas (NUs) inhibited GR activity in extracts of EMT-6/Ro cells was determined and compared to the magnitude of chemopotentiation realized when each was combined with MISO for the treatment of EMT-6/Ro cells in vitro. No correlation was observed between glutathione reductase inhibition and the potentiation of nitrosourea cytotoxicity by MISO in vitro, suggesting that inhibition of GR was not involved in the mechanism of MISO chemopotentiation. Furthermore, when the original correlation was re-examined with the inclusion of additional chemopotentiation data for four hydroxylated analogs of CCNU, including two which possess little or no lysine-carbamoylating activity but which were significantly enhanced by MISO, a correlation between carbamoylation and the magnitude of MISO chemopotentiation could not be established. From these studies we conclude that NU-carbamoylating activity is not the prime determinant of interaction between MISO and the NUs.
实验旨在确定谷胱甘肽还原酶（GR）的氨甲酰化相关抑制作用是否参与了先前报道的亚硝基脲氨甲酰化活性（由与L-赖氨酸的结合程度定义）与米索硝唑（MISO）化学增敏程度之间的相关性。测定了12种不同亚硝基脲（NUs）对EMT-6/Ro细胞提取物中GR活性的抑制程度，并将其与每种亚硝基脲与MISO联合用于体外治疗EMT-6/Ro细胞时实现的化学增敏程度进行比较。在体外，未观察到谷胱甘肽还原酶抑制与MISO对亚硝基脲细胞毒性的增敏作用之间存在相关性，这表明GR的抑制不参与MISO化学增敏的机制。此外，当重新审视原始相关性时，纳入了CCNU的四种羟基化类似物的额外化学增敏数据，其中包括两种几乎没有或没有赖氨酸氨甲酰化活性但被MISO显著增强的类似物，结果无法建立氨甲酰化与MISO化学增敏程度之间的相关性。从这些研究中我们得出结论，NU-氨甲酰化活性不是MISO与NUs之间相互作用的主要决定因素。
