Liver microsomal uptake of (14C)vinyl chloride and transformation to protein alkylating metabolites in vitro.
Liver microsomal uptake of (14C)vinyl chloride and transformation to protein alkylating metabolites in vitro.
复制标题
肝微粒体摄取 (14C) 氯乙烯并在体外转化为蛋白质烷基化代谢物。
DOI：
10.1016/0041-008x(76)90208-8
复制
发表时间：
1976
影响因子：
3.8
通讯作者：
W. Bolt
中科院分区：
文献类型：
--
作者：
H. Kappus;H. Kappus;H. Bolt;H. Bolt;A. Buchter;A. Buchter;W. Bolt;W. Bolt
[1,2-14C]氯乙烯气体与大鼠肝微粒体在全玻璃真空系统中一起孵育。测定了微粒体对氯乙烯放射性的摄取和不可逆蛋白质结合。微粒体对氯乙烯的吸收和氯乙烯代谢物对蛋白质的烷基化都取决于培养时间、酶活性微粒体、NADPH、氧气和氯乙烯在大气中的分压，并且可以被一氧化碳抑制。在存在 NADPH 的培养过程中，微粒体吸收的氯乙烯比不存在 NADPH 的情况多 10 倍。与不含 NADPH 的微粒体摄取相比，白蛋白溶液和脂质体悬浮液对氯乙烯的摄取处于相似的范围。将谷胱甘肽和细胞质级分添加到与 NADPH 一起孵育的微粒体中，导致微粒体对氯乙烯的摄取增加，并减少氯乙烯代谢物对蛋白质的烷基化。如果微粒体孵育中存在三氯丙烯氧化物，则氯乙烯代谢物引起的蛋白质烷基化反应增加两倍，而微粒体对氯乙烯的摄取不受影响。我们的结果与以下观点一致：微粒体吸收氯乙烯放射性是由于微粒体酶将氯乙烯气体转化为非挥发性代谢物，并且环氧乙烷可能是能够与蛋白质反应的氯乙烯的主要微粒体代谢物。
[1,2-14C]Vinyl chloride gas was incubated with rat liver microsomes in an all-glass vacuum system. Microsomal uptake and irreversible protein binding of vinyl chloride radioactivity was determined. Both uptake of vinyl chloride by microsomes and alkylation of proteins by vinyl chloride metabolites were dependent on incubation time, enzymatically active microsomes, NADPH, oxygen, and the partial pressure of vinyl chloride in the atmosphere, and could be inhibited by carbon monoxide. During incubation in presence of NADPH, 10 times more vinyl chloride was taken up by microsomes than in absence of NADPH. Uptake of vinyl chloride by albumin solutions and liposomal suspensions was in a similar range compared to the microsomal uptake without NADPH. Addition of glutathione and cytoplasmic fractions to microsomal incubations with NADPH led to an increase in microsomal uptake of vinyl chloride and to a decrease in protein alkylation by vinyl chloride metabolites. If trichloropropene oxide was present in the microsomal incubation, the protein alkylation reaction by vinyl chloride metabolites was increased twofold, while the microsomal uptake of vinyl chloride was not influenced. Our results are consistent with the view that the microsomal uptake of vinyl chloride radioactivity is due to transformation of vinyl chloride gas to nonvolatile metabolites by microsomal enzymes and that chloroethylene oxide might be the primary microsomal metabolite of vinyl chloride capable of reacting with proteins.