大鼠肝细胞核在异生物激活与失活中的致突变相关性。环磷酰胺和环氧氯丙烷对粟酒裂殖酵母和酿酒酵母的活性。

Mutagenic relevance of rat hepatocyte nuclei in the activation and inactivation of xenobiotica. Cyclophosphamide and epichlorohydrin activity on the yeasts S. pombe and S. cerevisiae.

作者信息

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

出版信息

Mutat Res. 1983 Nov;111(3):313-23. doi: 10.1016/0027-5107(83)90029-5.

Abstract

The influence on the mutagenicity of cyclophosphamide (Cy) and epichlorohydrin (ECH), of liver nuclei and hepatic post-mitochondrial (S9) preparations from phenobarbital-treated rats, was examined. The study was conducted in vitro, with 2 yeasts, Schizosaccharomyces pombe (P1 strain) which allows the detection of forward mutations, and Saccharomyces cerevisiae (D5 strain), in which the induction of different genetic effects, such as mitotic recombination, can be evaluated. The results indicated that the nuclear fraction has a qualitative capacity for biotransformation of compounds, overlapping that of S9. From a quantitative point of view, the Cy-activating capacity of the nuclear fraction was twice as high as that of S9 whereas the two fractions showed a similar ECH-inactivating ability. The present study strengthens the hypothesis of the relevance of nuclei as a site of metabolic activation and inactivation of exogenous compounds.

摘要

研究了苯巴比妥处理大鼠的肝细胞核和肝线粒体后组分（S9）制剂对环磷酰胺（Cy）和环氧氯丙烷（ECH）致突变性的影响。该研究在体外进行，使用了两种酵母，即粟酒裂殖酵母（P1菌株），可检测正向突变，以及酿酒酵母（D5菌株），可评估不同遗传效应如有丝分裂重组的诱导情况。结果表明，核组分具有对化合物进行生物转化的定性能力，与S9的能力重叠。从定量角度来看，核组分的Cy激活能力是S9的两倍，而两种组分显示出相似的ECH失活能力。本研究强化了细胞核作为外源性化合物代谢激活和失活位点相关性的假说。