De Oliveira A R, Machado-Santelli G M
Mutat Res. 1987 Feb;187(2):91-7. doi: 10.1016/0165-1218(87)90121-2.
The present study demonstrates that the antiepileptic drug diphenylhydantoin (DPH) is capable of inducing aneuploidy but not structural aberrations in cultured mouse embryonic fibroblasts. A high concentration of 200 micrograms/ml was found to increase the percentage of hyperdiploidy from 4.8 (control) to 16.0. The treatment was found to increase mitotic indices as a consequence of a mitotic-arresting action of the drug. These effects are probably due to the effect of the drug on the structure of the mitotic apparatus. Abnormal cell divisions and mitotic disturbance were found to increase in a dose-dependent manner after DPH treatment. In a parallel study, human amnion cells were found to show similar response to DPH treatment.
本研究表明,抗癫痫药物苯妥英(DPH)能够在培养的小鼠胚胎成纤维细胞中诱导非整倍体,但不能诱导结构畸变。发现200微克/毫升的高浓度可使超二倍体百分比从4.8(对照)增加到16.0。由于该药物的有丝分裂阻滞作用,发现该处理可增加有丝分裂指数。这些作用可能是由于该药物对有丝分裂器结构的影响。发现DPH处理后异常细胞分裂和有丝分裂紊乱以剂量依赖性方式增加。在一项平行研究中,发现人羊膜细胞对DPH处理表现出类似反应。