Esser K J, Kotlarek F, Habedank M, Mühler U, Mühler E
Hum Genet. 1981;56(3):345-8. doi: 10.1007/BF00274690.
In epileptic children the long-term therapy with anticonvulsant drugs is absolutely necessary. However, anticonvulsant drugs have been suspected to be mutagenic and teratogenic. To investigate this problem metaphase chromosome observations were performed using short-time culture of peripheral blood lymphocytes from twenty children. Ten of the children had been treated with phenytoin and the other ten with primidone on monotherapy. The long-term administration of anticonvulsant drugs was monitored by measurement of the serum concentrations of phenytoin and primidone, by seizure anamnesis, and by repeated EEG investigations. Analyzing 100 mitoses from each proband, we found no increase of structural or numerical aberrations in our patients compared with six controls. In adults, however, anticonvulsant drugs have been found to cause structural aberrations and chromosomal damage. The absence of these lesions in children may reflect the higher efficiency of DNA-repair in local DNA-damage.
对于癫痫患儿而言,长期使用抗惊厥药物进行治疗是绝对必要的。然而,抗惊厥药物一直被怀疑具有致突变性和致畸性。为了研究这个问题,我们对20名儿童外周血淋巴细胞进行短期培养,进而进行中期染色体观察。其中10名儿童接受苯妥英单一疗法治疗,另外10名儿童接受扑米酮单一疗法治疗。通过测量苯妥英和扑米酮的血清浓度、癫痫发作史以及反复进行脑电图检查来监测抗惊厥药物的长期使用情况。分析每个先证者的100个有丝分裂,我们发现与6名对照者相比,我们的患者中结构或数量畸变并未增加。然而,在成人中,抗惊厥药物已被发现会导致结构畸变和染色体损伤。儿童中不存在这些病变可能反映了局部DNA损伤时DNA修复的更高效率。