Advantage of the use of human liver S9 in the Ames test
Advantage of the use of human liver S9 in the Ames test
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DOI：
10.1016/s1383-5718(98)00159-4
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发表时间：
1999-01-02
影响因子：
1.9
通讯作者：
Satoh, T
中科院分区：
文献类型：
--
作者：
Hakura, A;Suzuki, S;Satoh, T
使用未处理（R-n）或用苯巴比妥/5，6-苯并咪唑酮（R-i）预处理的雄性Sprague-Dawley大鼠制备的人肝S9或肝S9，比较了13种化学品的致突变性。本研究中使用的供试化合物是公认的前致癌物，需要细胞色素P450进行代谢活化。这些包括多环芳烃、芳香胺、杂环芳香胺、亚硝基胺和硝基芘。我们使用了四种人肝S9组分，其中一种是从具有较高水平的P450催化药物代谢酶活性的肝脏样品中制备的，其可能的解释是抗哮喘药物诱导酶10年。本研究的结果如下：（1）使用的每种S9组分的前致癌物的致突变活性大小存在个体差异，（2）使用三种人S9组分观察到化学品的致突变性相当（H3、H8和H12），而人H14 S9组分显示出更高的P450酶活性，导致致突变性远高于其他三种人S9标本，（3）人和大鼠肝S9组分的前致癌物的致突变性的数量级为Ri大于或等于H14大于或等于Rn大于或等于H3、H8和H12，而2-氨基蒽、N-亚硝基二甲胺和1-硝基芘的致突变性的数量级为H3、H8、H12，并且H14大于或等于R11大于或等于R11。本研究中的实验数据强烈表明，在艾姆斯试验中补充使用人肝S9组分是一种比大鼠S9更有用的工具，用于评价对人体的遗传毒性。(C)1999 Elsevier Science B. V.保留所有权利。
The mutagenicity of 13 chemicals was compared using human liver S9 or liver S9 prepared from male Sprague-Dawley rats either non-treated (R-n) or pretreated with phenobarbital/5,6-benzoflavone (R-i), The test compounds used in this study were well recognized procarcinogens requiring cytochrome P450 for metabolic activation. These included polycyclic aromatic hydrocarbons, aromatic amines, heterocyclic aromatic amines, nitrosoamines, and nitropyrene. We used four human liver S9 fractions, one of which was prepared from the liver sample having higher levels of the P450-catalyzed drug metabolizing enzyme activities, a possible explanation for which was enzyme induction by anti-asthma agents for 10 years. The results of the present study are as follows: (1) there were individual differences in the magnitude of the mutagenic activity of the procarcinogens by each S9 fraction used, (2) equivalent mutagenicity of chemicals was seen with three human S9 fractions (H3, H8, and H12,), while a human H14 S9 fraction showed higher P450 enzyme activity, leading to much higher mutagenicity than the other three human S9 specimens, (3) the order of magnitude of the mutagenicity of the procarcinogens using human and rat liver S9 fractions was R-i greater than or equal to H14 greater than or equal to R-n greater than or equal to H3, H8, and H12, while with 2-aminoanthrathene, N-nitrosodimethylamine, and l-nitropyrene, this relationship was H3, H8, H12, and H14 greater than or equal to R-n greater than or equal to R-i. The experimental data in the present study strongly suggest that the complementary use of human liver S9 fraction in the Ames test is a much more useful tool than rat S9 for evaluation of genotoxicity to humans. (C) 1999 Elsevier Science B.V. All rights reserved.