脳障害児における抗てんかん薬の遺伝毒性　　姉妹染色分体交換の測定による検討

Sister chromatid exchange (SCE) implies a symmetrical exchange at one site between two chromatids of a chromosome. SCE is considered to be an indication of DNA damage and repair, and examination of SCE is widely used as a sensitive method for evaluating the mutagenicity of various chemical agents. We analyzed SCE in lymphocytes of forty-five brain-damaged children and ten healthy controls in order to assess whether antiepileptic drugs (AEDs) induce SCEs.<br>Twenty-three epileptic patients were treated with phenytoin (PHT), phenobarbital (PB) and other AEDs. Twenty-two non-epileptic patients were not given AEDs. 0.5ml of heparinized blood was added to 5 ml of RPMI-1640 medium supplemented with 20% fetal bovine serum and 296 phytohemagglutinin-M. Forty-eight hours after initiation of culture, bromodeoxyuridine (BrdU) was added at a concentration of 0.04μ/ml and the cultures were further incubated for twenty-four hours including final two-hour treatment with colcemid. Lymphocytes from five patients and three controls were also cultured in medium containing various concentrations of PHT or PB. The preparations were stained by BrdU-alkaline-Giemsa method. SCE was counted in 20 cells from each subject.<br>The frequency of SCE/cell was 5.52±1.29 (mean±SD) in epileptics, 5.52±1.75 in non-epileptics and 3.98±0.48 in controls. SCEs in both epileptics and non-epileptics were signifi-cantly higher than those in controls by t-tets. But there was no significant difference between epileptics and non-epileptics. In vitro studies showed, however, an increase of SCE with elevating levels of either PHT or PB in all subjects.<br>Although our results showed no clear evidence that AEDs by themselves induced SCEs in brain-damaged patients, an increased SCE frequency due to AED treatment in vitro might suggest their possible mutagenicity.