Casciano D A, Talaska G, Clive D
National Center for Toxicological Research, Division of Genetic Toxicology, Jefferson, AR 72079.
Mutat Res. 1991 Jun;263(2):127-32. doi: 10.1016/0165-7992(91)90070-k.
The antihistamine methapyrilene hydrochloride has been shown to be a potent hepatocarcinogen in Fischer 344 rats. It has also been evaluated in a number of short-term in vivo and in vitro genotoxicity assays with conflicting results. We studied its ability to form DNA adducts in the L5178Y/TK+/- mouse lymphoma cells, an assay system in which methapyrilene is a moderately active mutagen and appears to induce mutations predominantly of chromosomal origin. Methapyrilene failed to induce formation of DNA adducts in L5178Y cell DNA at doses which induced mutations at the thymidine kinase locus. These data suggest that methapyrilene induces mutations in this system through an indirect genotoxic mechanism; e.g., via an oxidative mechanism or interaction with chromosomal proteins.
抗组胺药盐酸美吡拉敏已被证明是Fischer 344大鼠的一种强效肝癌致癌物。它也在一些短期体内和体外遗传毒性试验中进行了评估，结果相互矛盾。我们研究了它在L5178Y/TK+/-小鼠淋巴瘤细胞中形成DNA加合物的能力，在这个检测系统中，美吡拉敏是一种中等活性的诱变剂，似乎主要诱导染色体起源的突变。在诱导胸苷激酶基因座发生突变的剂量下，美吡拉敏未能诱导L5178Y细胞DNA中形成DNA加合物。这些数据表明，美吡拉敏在该系统中通过间接遗传毒性机制诱导突变；例如，通过氧化机制或与染色体蛋白相互作用。
