Lee H K, Kim Y H, Roh J K
Toxicology Research Center, Korea Research Institute of Chemical Technology, Yuseong, Taejeon, South Korea.
Mutat Res. 1994 Dec;341(2):77-82.
The antihistaminic agent methapyrilene hydrochloride (MPH, CAS No. 135-23-9) has been reported as a potent rat hepatocarcinogen. However, neither the action mechanism nor mutagenicity of MPH have been clearly elucidated yet. Chromosomal aberration (CA) tests were performed with MPH in CHO-K1-BH4 and CHL cells without a metabolic activation system. Isochromatid break-like aberrations were observed in metaphases of CHO-K1-BH4 cells treated with MPH. MPH induced CA more effectively at higher pH in equitoxicity base. In contrast to CHO-K1-BH4 cells, typical chromatid type exchanges were observed in CHL cells treated with MPH. These results clearly support the results of other researchers that MPH induce chromosomal aberration and imply that MPH induces cancer in animal via other mechanisms than mere DNA damage or gene mutation which had been nearly proven to be negative by many researchers. It was suggested that pH variation might increase the sensitivity of CA tests for certain category of chemicals with dissociation potential.
抗组胺药盐酸美吡拉敏（MPH，化学物质登记号：135 - 23 - 9）已被报道为一种强效的大鼠肝癌致癌物。然而，MPH的作用机制和致突变性尚未得到明确阐释。在没有代谢活化系统的情况下，对MPH在CHO - K1 - BH4和CHL细胞中进行了染色体畸变（CA）试验。在用MPH处理的CHO - K1 - BH4细胞中期观察到了等染色单体断裂样畸变。在等毒性碱中，较高pH值时MPH诱导CA的效果更明显。与CHO - K1 - BH4细胞不同，在用MPH处理的CHL细胞中观察到了典型的染色单体型交换。这些结果明确支持了其他研究人员的结果，即MPH诱导染色体畸变，并暗示MPH通过许多研究人员几乎已证明为阴性的单纯DNA损伤或基因突变以外的其他机制在动物体内诱发癌症。有人提出，pH值变化可能会增加CA试验对某些具有解离潜力的化学物质的敏感性。
