卡马西平对癫痫患者染色体畸变率和姐妹染色单体交换频率的影响及与叶酸的关系

The relationship between the effect of carbamazepine on chromosome aberration rate and sister chromatid exchange frequencies and the folic acid in epileptic patients

目的 研究卡马西平 (CBZ)的诱变性及其与叶酸的关系 ,探讨CBZ致畸及叶酸防止致畸的机制。方法 应用细胞遗传学方法 ,检测 15例单服CBZ及 15例CBZ加叶酸的癫痫患者外周血淋巴细胞染色体畸变率 (CAR)、姐妹染色单体交换 (SCE)频率 ,同时用放免法测定血清叶酸含量 ,并与未服药癫痫对照组及正常对照组进行比较。结果 单服CBZ组患者的CAR和SCE频率较对照组增高 ,其血清叶酸含量较正常对照组下降 ;单服CBZ组患者的CAR和SCE频率较服CBZ加叶酸组增高 ;CBZ血药浓度与叶酸水平、CAR及SCE之间未发现明显相关性。结论 CBZ具有DNA损伤效应 ,其损伤效应可能与CBZ干扰叶酸代谢有关 ,补充叶酸可以有效防止CBZ引起的DNA损伤。

Objective To investigate the relationship between the mutagenicity of carbamazepine (CBZ) and folic acid (FA), and to explore the mechanism of CBZ teratogensis and the prevention effect of the folic acid. Methods Peripheral blood lymphocyte chromosome aberration rate (CAR), sister chromatid exchange (SCE)frequencies, and serum FA levels have been studied in 15 CBZ -treated epileptic patients, 15 CBZ plus FA-treated epileptic patients The untreated epileptic patients and the health subjects were served as controls Results CAR and SCE frequencies were significantly higher in CBZ group as compared with the CBZ plus FA group and the controls ( P <0 01) Serum FA levels were lower in CBZ group as compared with health controls ( P <0 01). Serum concentration of CBZ did not show correlation with FA,CAR and SCE. Conclusion CBZ may damage chromosome of the patients who received CBZ The chromosome damage induced by CBZ may be probably associated with interference of CBZ with folate metabolism, and the supplementation of FA may effectively prevent this damage