氯丙嗪和氯氮平对小鼠生殖细胞和人淋巴细胞的诱变效应

The effects of chlorpromazine and clozapine on the germ cells of mice and the lymphocytes of human

为探讨氯丙嗪和氯氮平在使用临床治疗剂量时的遗传毒理效应，研究了两药对小鼠生殖细胞和小鼠子代体细胞的影响，以及对人体淋巴细胞姊妹染色单体互换（ＳＣＥ）频率及微核率的影响。结果显示：（１）连续给药５天后第１周两药高、中、低三个剂量组均能引起小鼠精子头部畸形率明显增高，但停药４周后对精子的致畸作用基本消失；（２）两药对小鼠睾丸细胞及子代体细胞的染色体结构畸变率均无明显影响；（３）两药在治疗剂量时对人淋巴细胞的ＳＣＥ频率及微核率无明显影响，治疗前后的自身对照研究亦未见两频率有明显改变；（４）两药的血药浓度与ＳＣＥ频率及微核率之间无量效关系。研究结果提示，两药在临床治疗剂量时对小鼠生殖细胞染色体结构以及对人体遗传物质均无明显损伤作用。

The purpose of this study was to investigate (1)the effect of chlorpromazine (CPZ) and clozapine (PLZ) on the germ cells of mice, (2) their effect on the rates of sister chromatid exchange (SCE) and micronucleus (MN) of human's lymphocytes. The results were: (1) After oral CPZ or CLP in high (CPZ 1000 mg/kg or CLZ 6.67 mg/kg) medium (CPZ 5 mg/kg or CLZ 3.33 mg/kg) or low (CPZ 2.50 mg/kg or CLZ 1.67 mg/kg) dosages were given daily for 5 days to different groups of mice, the morphological abnormal rates of the head of sperm cells in all experimental groups were significantly higher than that in the control group. (2) Either CPZ or CLZ had no significant effect on the chromosomal structure of both the germ cells of parent mice and the somatic cells of the next generation. (3) No significant effect on the rates of SCE or MN of human's lymphocytes was found when CPZ or CLZ was used in therapeutic dosages. (4) Through the assessment of the correlation of plasma concentration of CPZ and SCE MN, no dosageresponse relationship was found. The results showed that therapeutic dosage of CPZ or CLZ had no significant damage to the structure of mice germ cells or human lymphocytes.