림프구에 대한 clozapine의 생체내 유전독성

Abstract

Objective ■ Many drugs and environmental chemicals can induce aneuploidy or chromosome instability in vivo or in vitro. Modification of the fidelity of cellular division may occur via a variety of mechanisms and chemical interactions. The clozapine is new antipsychotic drug with superior effect than classic antipsychotics. But, it may produce agranulocytosis and seizure in some patients. Agranulocytosis is a serious side effect of this drug but the cause and mechanism of this side effect is not clearly explained. Some study suggested that oxidative stress can induce chromosome aberration and the other study suggested that clozapine produce free radical and it can induce oxidative stress on some kind of cells. Therefore we decided to investigate whether clozapine and its metabolites can induce genotoxic effect in vivo. Method : The patients were chronic schizophrenic patients without a treatment at least one year. Diagnosis was made by DSM-IV criteria and agreed by both of two psychiatrists. Blood sampling was done before the treatment and during the treatment with considerable time interval. We used peripheral blood lymphocyte culture method and we counted the numerical aberrations, sister chromatid exchanges. Results ; Chromosome aberration was not detected in all samples. Conclusion - Clozapine did not induce spontaneous chromosome aberration to human lymphocytes in vivo.