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在微生物系统中评估致癌物和非致癌物的致突变性及DNA修饰活性。

Evaluation of the mutagenicity and DNA-modifying activity of carcinogens and noncarcinogens in microbial systems.

作者信息

Rosenkranz H S, Poirier L A

出版信息

J Natl Cancer Inst. 1979 Apr;62(4):873-92.

PMID:372656
Abstract

The mutagenicity of 99 chemicals was determined in a standard Salmonella typhimurium assay with the use of strains TA1535 and TA1538; the DNA-modifying capacity was determined with normal and DNA polymerase-deficient Escherichia coli strains. The following categories of chemicals were studied: alkylating agents (15); nitrosamines, hydrazines, and related substances (8); heterocyclics (10); aromatic amines (36); polycyclic aromatic hydrocarbons (11); amides, ureas, and acylating agents (7); antimetabolites (5); inorganics (4); and promoters (3). Of the substances studied, 21 were known noncarcinogens, 21 were ultimate carcinogens, and 45 were procarcinogens. Of the noncarcinogens, 35, 30, and 25% were positive in the Salmonella, E. coli, and both systems, respectively. All of the ultimate carcinogens were detectable as mutagens of DNA-modifying agents; 79, 100, and 79% gave positive tests in the Salmonella, E. coli, and both systems, respectively. Of the procarcinogens 72% were identifiable by these procedures: 52, 67, and 48% in the Salmonella, E. coli, and both assays, respectively. A tabulation of the combined data for ultimate carcinogens and procarcinogens indicates that 77% of the carcinogens gave positive results: 61, 74, and 59% in the Salmonella, E. coli, and both assays, respectively. We suggest that, for prescreening procedures with microbial assays, S. typhimurium strains TA98 and TA100 be included and the standard E. coli DNA polymerase-deficient assay be run in tandem with the Salmonella mutagenicity assay. When the standard E. coli DNA polymerase-deficient assay does not give interpretable results because of the lack of zones of growth inhibition, a modified assay with the use of liquid suspension should be performed.

摘要

利用鼠伤寒沙门氏菌TA1535和TA1538菌株,通过标准试验测定了99种化学物质的致突变性;利用正常和缺乏DNA聚合酶的大肠杆菌菌株测定了DNA修饰能力。研究了以下几类化学物质:烷基化剂(15种);亚硝胺、肼及相关物质(8种);杂环化合物(10种);芳香胺(36种);多环芳烃(11种);酰胺、脲和酰化剂(7种);抗代谢物(5种);无机物(4种);以及促癌剂(3种)。在所研究的物质中,21种为已知的非致癌物,21种为直接致癌物,45种为前致癌物。在非致癌物中,分别有35%、30%和25%在沙门氏菌试验、大肠杆菌试验以及两种系统中呈阳性。所有直接致癌物均可检测为DNA修饰剂的诱变剂;分别有79%、100%和79%在沙门氏菌试验、大肠杆菌试验以及两种系统中检测呈阳性。在前致癌物中,72%可通过这些程序鉴定出来:在沙门氏菌试验、大肠杆菌试验以及两种试验中分别为52%、67%和48%。直接致癌物和前致癌物综合数据的列表表明,77%的致癌物检测呈阳性:在沙门氏菌试验、大肠杆菌试验以及两种试验中分别为61%、74%和59%。我们建议,在微生物试验的预筛选程序中,应纳入鼠伤寒沙门氏菌TA98和TA100菌株,并将标准的缺乏DNA聚合酶的大肠杆菌试验与沙门氏菌致突变性试验串联进行。当标准的缺乏DNA聚合酶的大肠杆菌试验由于缺乏生长抑制区而无法得出可解释的结果时,应采用液体悬浮法进行改良试验。

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