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[短期试验及构效关系模型评估化学物质致癌性的效率]

[Efficiency of evaluating the carcinogenicity of chemical substances in short-term tests and the SAR model].

作者信息

Tarasov V A, Tsarenko N A, Mel'nik V A, Mustafaev O N, Makedonov G P, Tarasov A V

出版信息

Genetika. 2009 Dec;45(12):1674-84.

Abstract

The efficiency of estimating the carcinogenic activity of chemical substances was compared for five short-term tests and structure-activity relationships (SAR) analysis. The sample included 84 substances with known biological testing results obtained by the Ames test, bacterial SOS chromotest (SOS), chromosome aberration (CA) cytogenetic test, sister chromatid exchange (SHE) test, and gene mutation (GM) test with mammalian cells in vitro and by carcinogenicity assays in rodents in vivo. Structural descriptors were selected using an original database, which included the structural formulas of substances with known carcinogenic activity in rodents. Original software was created to generate and select the descriptors that statistically coincided with carcinogenic activity. The descriptors that were associated exclusively with carcinogenic substances from the database and the tests that produced positive results exclusively with carcinogens were used to evaluate the carcinogenic activity of the substances. A combination of three short-term tests (Ames, SOS, and CA tests) and the SAR model proved to identify carcinogenicity for more than 60% of carcinogens.

摘要

对五种短期试验和构效关系(SAR)分析评估化学物质致癌活性的效率进行了比较。样本包括84种物质,这些物质具有通过艾姆斯试验、细菌SOS显色试验(SOS)、染色体畸变(CA)细胞遗传学试验、姐妹染色单体交换(SHE)试验、体外哺乳动物细胞基因突变(GM)试验以及啮齿动物体内致癌性试验获得的已知生物学测试结果。使用一个原始数据库选择结构描述符,该数据库包含在啮齿动物中具有已知致癌活性的物质的结构式。创建了原始软件以生成和选择与致癌活性在统计学上相符的描述符。仅与数据库中的致癌物质相关联的描述符以及仅对致癌物产生阳性结果的试验用于评估这些物质的致癌活性。三种短期试验(艾姆斯试验、SOS试验和CA试验)与SAR模型相结合,被证明能够识别超过60%的致癌物的致癌性。

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