Genotoxic Effects of Antiepileptic Drugs on Brain-damaged Children Measured by Sister Chromatid Exchange

• Published in: Japanese Journal of National Medical Services Vol. 41; no. 4; pp. 350 - 355
• Main Authors: YAMAMOTO, Katsuya, KONOSU, Takeshi, NAKAGAWARA, Kanichi, SAKAI, Kyoko, NUMATA, Yukiko, SATO, Gen
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of National Medical Services 1987; 一般社団法人 国立医療学会
• Subjects: 変異原性; 姉妹染色分体交換(SCE); 抗てんかん薬; 脳障害児
• ISSN: 0021-1699; 1884-8729
• DOI: 10.11261/iryo1946.41.350

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. 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. 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. 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.