Mitchell A D, Auletta A E, Clive D, Kirby P E, Moore M M, Myhr B C
Genesys Research, Incorporated, Research Triangle Park, NC 27709, USA.
Mutat Res. 1997 Nov 27;394(1-3):177-303. doi: 10.1016/s1383-5718(97)00115-0.
The L5178Y/tk+/- (-)3.7.2C mouse lymphoma assay (MLA) which detects mutations affecting the heterozygous thymidine kinase (tk) locus is capable of responding to chemicals acting as clastogens as well as point mutagens. Improvements in the assay to enhance detection of this spectrum of genetic events are summarized, and criteria for evaluating the data are defined. Using these criteria, the Phase III Work Group reviewed and evaluated literature containing MLA results published from 1976 through 1993. The data base included 602 chemicals of which 343 were evaluated as positive, 44 negative, 18 equivocal, 54 apparently inappropriate for evaluation in this test system with the published protocols, and 142 that were inadequately tested, and thus a definitive call could not be made. The overall performance of the assay is summarized by chemical class, and the outcome of testing 260 chemicals in the MLA is compared with Gene-Tox and National Toxicology Program evaluations of rodent carcinogenesis bioassay results for the same chemicals. Based on the Work Group's evaluation of published MLA data for chemicals that were considered adequately tested, it is concluded that for most chemicals the L5178Y/tk+/- mouse lymphoma assay is eminently well suited for genotoxicity testing and for predicting the potential for carcinogenicity.
L5178Y/tk+/- (-)3.7.2C小鼠淋巴瘤试验（MLA）可检测影响杂合胸苷激酶（tk）位点的突变，能够对作为断裂剂和点突变剂的化学物质作出反应。本文总结了该试验为增强对这类遗传事件的检测所做的改进，并定义了评估数据的标准。第三阶段工作组依据这些标准，对1976年至1993年间发表的包含MLA结果的文献进行了审查和评估。数据库涵盖602种化学物质，其中343种评估为阳性，44种为阴性，18种为可疑，54种根据已发表的方案在该测试系统中明显不适于评估，142种测试不充分，因此无法做出明确判定。试验的总体性能按化学类别进行了总结，并将MLA中260种化学物质的测试结果与基因毒性计划和国家毒理学计划对相同化学物质的啮齿动物致癌生物测定结果评估进行了比较。基于工作组对已充分测试的化学物质的已发表MLA数据的评估，得出结论：对于大多数化学物质，L5178Y/tk+/-小鼠淋巴瘤试验非常适合进行遗传毒性测试和预测致癌潜力。
