环氧氯丙烷（ECH）遗传毒性的评估。体外裂殖酵母中微粒体环氧化物水解酶依赖性环氧氯丙烷致突变性的失活。

Evaluation of epichlorohydrin (ECH) genotoxicity. Microsomal epoxide hydrolase-dependent deactivation of ECH mutagenicity in Schizosaccharomyces pombe in vitro.

作者信息

Rossi A M, Migliore L, Loprieno N, Romano M, Salmona M

出版信息

Mutat Res. 1983 Apr;109(1):41-52. doi: 10.1016/0027-5107(83)90093-3.

Abstract

The mutagenic effect of epichlorohydrin (ECH) on the yeast Schizosaccharomyces pombe was studied in vitro in the presence of mouse-liver S9 mix and microsomal and cytosolic fractions. The incubations were always performed in the absence of NADPH-generating systems. S9 mix and microsomes from phenobarbital-pretreated mice significantly reduced ECH mutagenicity, whereas the cytosol did not result in any deactivating effect. The various protein contents of the subcellular fractions were not involved in any scavenger effect as regards ECH mutagenic activity. Moreover, the addition of reduced glutathione to the incubation mixtures indicated that it did not play an important role, either per se or through the enzyme(s) glutathione-S-epoxide transferase(s), in preventing ECH genotoxicity. Our results suggest that microsomal epoxide hydrolase(s) represents the major step in the detoxifying pathway of ECH. These observations were supported by measurements of the specific epoxide hydrolase activity in the various fractions on the same substrate.

摘要

在存在小鼠肝脏S9混合液、微粒体和胞质组分的情况下，在体外研究了环氧氯丙烷（ECH）对粟酒裂殖酵母的诱变作用。孵育总是在没有NADPH生成系统的情况下进行。来自苯巴比妥预处理小鼠的S9混合液和微粒体显著降低了ECH的诱变性，而胞质溶胶未产生任何失活作用。亚细胞组分的各种蛋白质含量与ECH诱变活性的任何清除作用均无关。此外，向孵育混合物中添加还原型谷胱甘肽表明，它本身或通过谷胱甘肽-S-环氧化物转移酶在预防ECH遗传毒性方面均未发挥重要作用。我们的结果表明，微粒体环氧化物水解酶是ECH解毒途径中的主要步骤。通过测量各组分对同一底物的特异性环氧化物水解酶活性，这些观察结果得到了支持。