Nagao T
Mutat Res. 1987 Mar;177(1):171-8. doi: 10.1016/0027-5107(87)90032-7.
ICR strain male mice were injected intraperitoneally with daily doses of MNU (5-25 mg/kg) for 5 days and mated to untreated virgin females of the same strain on days 1-7, 8-14, 15-21 and 64-80 after the last dose. Copulations during these periods involve, respectively, spermatozoa, late spermatids, early spermatids, and spermatogonial stem cells at the time of the last treatment. The uterine contents were examined on day 18 of pregnancy for post-implantation losses (dominant lethality). Fetuses were examined for external and skeletal abnormalities. In contrast to the results reported for specific-locus mutations, MNU treatment of either postmeiotic cells or spermatogonial stem cells caused dose-dependent significant increases in the incidence of congenital defects and of dominant lethals over the control levels. The relative sensitivity of germ cells sampled on days 1-7, 8-21 and 64-80 to MNU-induced congenital defects was 1:1.6:2. For the induction of dominant lethals, the sensitivity ratio was 1:1.8:0.5. It is proposed that congenital defects in the offspring of mice following paternal treatment with MNU may represent mostly chromosomal rather than genic changes. Cleft palate was the most frequent of the external abnormalities, which were significantly induced in every treatment series; fused ribs were the most frequent of the skeletal abnormalities, which were significantly induced in the treatment series for spermatogonial stem cells.
将ICR品系雄性小鼠腹腔注射每日剂量的N-甲基-N-亚硝基脲（MNU，5-25毫克/千克），持续5天，并在最后一剂后的第1-7天、8-14天、15-21天和64-80天与同一品系未经处理的处女雌性交配。这些时期的交配分别涉及最后一次处理时的精子、晚期精子细胞、早期精子细胞和精原干细胞。在妊娠第18天检查子宫内容物，以确定植入后损失（显性致死率）。检查胎儿的外部和骨骼异常情况。与特定位点突变的报告结果相反，用MNU处理减数分裂后细胞或精原干细胞会导致先天性缺陷和显性致死率的发生率比对照水平有剂量依赖性的显著增加。在第1-7天、8-21天和64-80天采集的生殖细胞对MNU诱导的先天性缺陷的相对敏感性为1:1.6:2。对于显性致死的诱导，敏感性比率为1:1.8:0.5。有人提出，父本用MNU处理后小鼠后代的先天性缺陷可能主要代表染色体而非基因变化。腭裂是最常见的外部异常，在每个处理系列中均有显著诱导；肋骨融合是最常见的骨骼异常，在精原干细胞处理系列中显著诱导。
