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阿霉素对小鼠体细胞和生殖细胞的遗传毒性作用。

The genotoxic effects of adriamycin in somatic and germinal cells of the mouse.

作者信息

Au W W, Hsu T C

出版信息

Mutat Res. 1980 Dec;79(4):351-61. doi: 10.1016/0165-1218(80)90160-3.

DOI:10.1016/0165-1218(80)90160-3
PMID:7442704
Abstract

The genotoxic effects of adriamycin on somatic and germinal cells were studied in mice treated with single injections of 3, 12 or 24 mg/kg of the drug. From 1 to 5 days post-injection, chromosome aberrations were observed in bone-marrow cells and in diakineses-metaphase I cells from the testes. The frequency of chromosome breakages peaked at 5 h or 1 day for the bone marrow and at 3 and 5 days for the testis. Univalent formation was increased overall but did not have a dose- and time-dependent relationship. In long-term follow-up studies, adriamycin was found to induce cell killing of germline cells which resulted in a reduction in the numbers of spermatocytes and sperm from mice treated with the higher doses. There was complete absence of gametogenetic elements and, eventually, testicular atrophy occurred. In mice treated with 3 mg/kg, there was gradual recovery of spermatogenesis from 50 days onward. Chromosome breaks and translocations were again observed in the recovering spermatocytes. It was concluded that some of the chromosome aberrations must have been induced in the spermatogonial cells which had survived.

摘要

研究了阿霉素对经单次注射3、12或24mg/kg该药物处理的小鼠体细胞和生殖细胞的遗传毒性作用。在注射后1至5天,观察到骨髓细胞和睾丸双线期-中期I细胞中的染色体畸变。染色体断裂频率在骨髓中于5小时或1天达到峰值,在睾丸中于3天和5天达到峰值。单价体形成总体上增加,但没有剂量和时间依赖性关系。在长期随访研究中,发现阿霉素可诱导生殖系细胞的细胞杀伤,导致接受较高剂量处理的小鼠精母细胞和精子数量减少。完全没有配子发生成分,最终发生睾丸萎缩。在接受3mg/kg处理的小鼠中,从50天起精子发生逐渐恢复。在恢复的精母细胞中再次观察到染色体断裂和易位。得出的结论是,一些染色体畸变一定是在存活的精原细胞中诱导产生的。

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