Henry B, Grant S G, Klopman G, Rosenkranz H S
Department of Environmental and Occupational Health, University of Pittsburgh, PA 15238, USA.
Mutat Res. 1998 Feb 2;397(2):313-35. doi: 10.1016/s0027-5107(97)00231-5.
A database of 209 chemicals tested for induction of forward mutations at the heterozygous thymidine kinase (TK +/-) locus in L5178Y mouse lymphoma cells was analyzed for structure-activity relationships using the MultiCASE expert system. Consistent with evidence of several contributing biological mechanisms, these studies suggest that such mutations may occur by more than one mechanism. As might be expected, there was evidence for a component involving direct electrophilic attack on the cellular DNA, in a manner previously established as causative in the induction of mutations in Salmonella. In addition, however, there was also strong evidence for another mechanism or mechanisms involving chromosome missegregation, cellular toxicity or an alternate site of action, such as the microtubules.
利用MultiCASE专家系统，分析了一个包含209种化学物质的数据库，这些化学物质在L5178Y小鼠淋巴瘤细胞的杂合胸苷激酶（TK +/-）位点进行了正向突变诱导测试。与多种生物学机制的证据一致，这些研究表明，此类突变可能通过多种机制发生。正如预期的那样，有证据表明存在一种机制，涉及对细胞DNA的直接亲电攻击，其方式与先前在沙门氏菌中诱导突变的原因相同。然而，此外，也有强有力的证据表明存在另一种或多种机制，涉及染色体错分离、细胞毒性或其他作用位点，如微管。
