Awara W M, El-Gohary M, El-Nabi S H, Fadel W A
Department of Pharmacology and Toxicology, College of Pharmacy, University of Tanta, Egypt.
Toxicology. 1998 Jan 16;125(1):45-52. doi: 10.1016/s0300-483x(97)00160-1.
The mutagenic potential of carbamazepine (CBZ) therapy has been evaluated both in vivo and in vitro. Analysis of chromosome aberrations (CA), sister chromatid exchanges (SCEs), mitotic and proliferation indices (PRI) were performed. The in vivo study was carried out on 30 patients with idiopathic epilepsy end undergoing treatment with CBZ for different periods starting from 6 months up to 15 years. Plasma CBZ levels were also determined for each patient. The results showed that the total CA and SCEs were significantly increased in CBZ-treated patients. There was no significant correlation between CA and either duration of treatment or the plasma CBZ levels for each patient. The mitotic and proliferation indices were found to be slightly but non-significantly decreased compared to control values. On the other hand, in vitro analysis showed a significant dose-dependent increase in CA and SCEs in human lymphocyte cultures treated with CBZ (4-12 microg/ml). The mitotic and proliferation indices were also found to be decreased but only significantly in case of high doses of CBZ (12 microg/ml). Pretreatment of human lymphocytes with melatonin (0.5 mM) exhibited a significant decrease in the frequencies of CBZ-induced CA and SCEs as compared with non-treated cultures. The depressed mitotic and proliferation indices were also found to be improved in cultures pretreated with melatonin. In conclusion, these observations suggest that CBZ monotherapy may lead to chromosome damaging effects (genotoxic) and the use of melatonin as anti-mutagenic agent for human protection against CBZ-induced chromosome damage should be considered.
已在体内和体外评估了卡马西平（CBZ）治疗的致突变潜力。进行了染色体畸变（CA）、姐妹染色单体交换（SCE）、有丝分裂和增殖指数（PRI）的分析。体内研究针对30例特发性癫痫患者进行，这些患者正在接受CBZ治疗，治疗时间从6个月到15年不等。还测定了每位患者的血浆CBZ水平。结果显示，接受CBZ治疗的患者中，总CA和SCE显著增加。CA与每位患者的治疗持续时间或血浆CBZ水平之间均无显著相关性。与对照值相比，有丝分裂和增殖指数略有下降，但无统计学意义。另一方面，体外分析显示，用CBZ（4 - 12微克/毫升）处理的人淋巴细胞培养物中，CA和SCE呈显著的剂量依赖性增加。有丝分裂和增殖指数也有所下降，但仅在高剂量CBZ（12微克/毫升）时显著下降。用褪黑素（0.5毫摩尔）预处理人淋巴细胞后，与未处理的培养物相比，CBZ诱导的CA和SCE频率显著降低。在用褪黑素预处理的培养物中，有丝分裂和增殖指数降低的情况也有所改善。总之，这些观察结果表明，CBZ单一疗法可能导致染色体损伤效应（遗传毒性），应考虑使用褪黑素作为抗诱变剂来保护人类免受CBZ诱导的染色体损伤。
