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顺二氨二氯铂的致断裂效应。II. 对小鼠初级精母细胞和精原干细胞染色体畸变的诱导作用

Clastogenic effects of cis-diamminedichloroplatinum. II. Induction of chromosomal aberrations in primary spermatocytes and spermatogonial stem cells of mice.

作者信息

Adler I D, el Tarras A

机构信息

GSF-Institut für Säugetiergenetik, Neuherberg, F.R.G.

出版信息

Mutat Res. 1990 Mar;243(3):173-8. doi: 10.1016/0165-7992(90)90087-z.

DOI:10.1016/0165-7992(90)90087-z
PMID:2308596
Abstract

The clastogenic effect of the anticancer drug cis-diamminedichloroplatinum (II) (cisplatin) on meiotic prophase in primary spermatocytes and on spermatogonial stem cells of male (101/E1 x C3H/E1)F1 mice was studied. The intraperitoneal doses of cisplatin tested were 5.0, 7.5 and 10.0 mg/kg. Chromosomal aberrations were examined at diakinesis-metaphase 1 of meiosis 1-13 days after treatment, representing cells treated at diplotene, pachytene, zygotene, leptotene an preleptotene. Reciprocal translocations were evaluated 63-70 days after treatment, representing treated stem-cell spermatogonia. Cisplatin had a toxic effect in zygotene to preleptotene of meiosis, as indicated by the significant reduction in testicular weight. At diplotene, pachytene and zygotene no enhancement of aberrations was found. An increase in aberrant cells was observed during leptotene with preleptotene being the most sensitive stage. The dose-response relationship for aberrant cells was linear on day 13 after treatment. It is concluded that, like mitomycin C (Adler, 1976), cisplatin primarily caused aberrations during the premeiotic phase of DNA synthesis. No significant increase of translocation multivalents was found after treatment of stem-cell spermatogonia.

摘要

研究了抗癌药物顺式二氨二氯铂(II)(顺铂)对雄性(101/E1×C3H/E1)F1小鼠初级精母细胞减数分裂前期及精原干细胞的致断裂效应。所测试的顺铂腹腔注射剂量为5.0、7.5和10.0mg/kg。在处理后1 - 13天的减数分裂I终变期 - 中期I检查染色体畸变,这些细胞分别处于双线期、粗线期、偶线期、细线期和前细线期时接受处理。在处理后63 - 70天评估相互易位,代表处理过的干细胞精原细胞。顺铂对减数分裂的偶线期到前细线期有毒性作用,表现为睾丸重量显著减轻。在双线期、粗线期和偶线期未发现畸变增加。在细线期观察到异常细胞增加,前细线期是最敏感阶段。处理后第13天,异常细胞的剂量 - 反应关系呈线性。结论是,与丝裂霉素C(阿德勒,1976年)一样,顺铂主要在减数分裂前的DNA合成阶段引起畸变。处理干细胞精原细胞后未发现易位多价体显著增加。

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