Casciano D A, Shaddock J G, Talaska G
National Center for Toxicological Research, Division of Genetic Toxicology, Jefferson, AR 72079.
Mutat Res. 1988 Jul;208(3-4):129-35. doi: 10.1016/0165-7992(88)90048-6.
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 vitro genotoxicity assays resulting in conflicting reports. Short-term in vivo assays suggest that it may act as a promoter. We studied its ability to form DNA adducts in the target organ using the highly sensitive 32P-postlabeling technique. Methapyrilene failed to induce formation of DNA adducts in hepatocellular DNA at doses which induced S-phase DNA synthesis. These data suggest that methapyrilene does not induce the carcinogenesis process through a direct genotoxic mechanism.
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。它也在一些短期体外遗传毒性试验中进行了评估，结果报告相互矛盾。短期体内试验表明它可能起促癌剂的作用。我们使用高度灵敏的32P后标记技术研究了它在靶器官中形成DNA加合物的能力。在诱导S期DNA合成的剂量下，美吡拉敏未能诱导肝细胞DNA中DNA加合物的形成。这些数据表明，美吡拉敏不会通过直接的遗传毒性机制诱导致癌过程。
