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苯并(a)芘代谢对正常及葡萄糖-6-磷酸脱氢酶缺乏的人成纤维细胞中NADPH库的依赖性。

Dependence of benzo(a)pyrene metabolism on NADPH pool in normal and glucose-6-phosphate dehydrogenase deficient human fibroblasts.

作者信息

Pascale R, Ruggiu M E, Simile M M, Daino L, Vannini G, Seddaiu M A, Satta G, Feo F

机构信息

Istituto di Patologia Generale dell'Università di Sassari, Italy.

出版信息

Res Commun Chem Pathol Pharmacol. 1990 Sep;69(3):361-4.

PMID:2236903
Abstract

Human skin fibroblasts (HSF), from normal donors and donors carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase, grown in vitro in the presence of 0.25-5 microM benzo(a)pyrene (BaP), produced the following organic-soluble metabolites: 9,10-diol, 7,8-diol, quinones, 3- and 9-hydroxide and a more polar fraction, and the following water-soluble metabolites: more polar, 3- and 9-hydroxide and 9,10-diol. Single organic- and water-soluble metabolites increased with BaP concentration in both types of HSF, but the ratio normal/variant increased with BaP concentration. NADPH level and NADPH/NADP+ ratio underwent a slight decrease in normal HSF incubated with 2.5 microM BaP, while a greater fall occurred in the deficient HSF at 0.25 and 2.5 microM BaP. NADPH content seems to be rate-limiting for BaP metabolism in the deficient cells.

摘要

来自正常供体以及携带葡萄糖-6-磷酸脱氢酶地中海变体供体的人皮肤成纤维细胞(HSF),在0.25 - 5微摩尔苯并(a)芘(BaP)存在的情况下于体外培养,产生了以下有机可溶性代谢产物:9,10 - 二醇、7,8 - 二醇、醌、3 - 和9 - 羟基化合物以及一个极性更强的组分,还有以下水溶性代谢产物:极性更强的物质、3 - 和9 - 羟基化合物以及9,10 - 二醇。在两种类型的HSF中,单一有机可溶性和水溶性代谢产物均随BaP浓度增加而增加,但正常/变体的比例随BaP浓度增加。在与2.5微摩尔BaP孵育的正常HSF中,NADPH水平和NADPH/NADP⁺比例略有下降,而在0.25和2.5微摩尔BaP处理的缺陷型HSF中下降幅度更大。NADPH含量似乎是缺陷细胞中BaP代谢的限速因素。

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