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盐酸N-异丙基-α-(2-甲基肼基)-对甲苯酰胺(盐酸丙卡巴肼)对小鼠生殖组织的作用:显性致死效应

Action of N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide hydrochloride (procarbazine hydrochloride) in the germ tissue of mice: dominant lethal effects.

作者信息

Roberts G T, Johnson F M, Malling H V, Sharma R K

出版信息

Arch Toxicol. 1979 Feb 23;41(4):287-94. doi: 10.1007/BF00296898.

DOI:10.1007/BF00296898
PMID:435078
Abstract

A study was carried out on the effects of N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide (procarbazine, Natulan) in the dominant lethal test in the mouse. Male mice were dosed once and mated with fresh virgin females each week. The utilization of sperm, treated as spermatids or testicular sperm with 100-800 mg/kg, resulted in significant post- and pre-implantation death of embryos. Fertility was markedly reduced after the injection of 200 mg/kg of procarbazine and over. This is probably due to a cell killing effect, the most sensitive stages being differentiating spermatogonia, type A sermatogonia and resting primary spermatocytes. Total sterility was induced for several weeks with doses of 600 and 800 mg/kg. Up to 12 weeks after treatment the number of females with implants was still significantly lower than controls indicating a severe depletion of spermatogonial cells. The spectrum of effects correlates well with the drug's effect on nucleic acid and protein synthesis.

摘要

一项关于N-异丙基-α-(2-甲基肼基)-对甲苯酰胺(丙卡巴肼,纳突兰)对小鼠显性致死试验影响的研究。雄性小鼠单次给药,每周与新的未交配过的雌性小鼠交配。用100 - 800mg/kg剂量处理的精子(视为精子细胞或睾丸精子),导致胚胎着床后和着床前显著死亡。注射200mg/kg及以上剂量的丙卡巴肼后,生育力明显降低。这可能是由于细胞杀伤作用,最敏感的阶段是分化中的精原细胞、A型精原细胞和静止的初级精母细胞。600mg/kg和800mg/kg剂量可导致数周的完全不育。治疗后长达12周,有植入物的雌性小鼠数量仍显著低于对照组,表明精原细胞严重耗竭。效应谱与该药物对核酸和蛋白质合成的影响密切相关。

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