Nomura T
Department of Radiation Biology, Faculty of Medicine, Osaka University, Japan.
Mutat Res. 1988 Apr;198(2):309-20. doi: 10.1016/0027-5107(88)90008-5.
A large and significant increase of phenotypical anomalies was observed in the progeny of ICR parent mice treated before mating with X-rays, urethane, 7,12-dimethylbenz[a]anthracene, ethylnitrosourea (ENU), and 4-nitroquinoline 1-oxide, but the increase was not significant with furylfuramide. Major types of induced anomalies were cleft palate, dwarf, open eyelid, tail anomalies, and exencephalus. Dwarf, open eyelid and tail anomalies were predominant types of viable anomalies and were inherited as if they were dominant mutations with varying expressivity or penetrance. Incidence of prenatal anomalies increased with treated doses of X-rays, urethan, or ENU for both spermatozoa and spermatogonia. Spermatogonia were less sensitive to X-rays and urethane than spermatozoa, while ENU induced a very high incidence of prenatal anomalies by the spermatogonial treatment. In contrast to the previous works with X-rays, there was a clear, almost linear increase of anomalies in the dose range from 0 to 216 rad after spermatogonial exposure. For treatment of oocytes, there was also a clear increase with doses of X-rays and urethane. Doubling doses of X-rays for prenatal anomalies were 12 rad for spermatozoa, 27 rad for spermatogonia, and 19 rad for mature oocytes. These values are similar to those for ordinary mouse mutations. However, the mean rate of prenatal anomalies per rad (1.2 X 10(-4), 6.6 X 10(-5) and 9.1 X 10(-5) for spermatozoa, spermatogonia and mature oocytes, respectively) and that for 1 micrograms/g of ENU (3.4 X 10(-4) for spermatogonia) were 4-40 times higher than that of ordinary mutation in mice, because overall phenotypical abnormalities were scored in this study. Information obtained from the work on phenotypical anomalies is valuable to assess genetic risk of radiation and chemicals, because a majority of human genetic diseases show this kind of irregular and uncertain inheritance and most of the induced anomalies are similar to those found in humans.
在与X射线、氨基甲酸乙酯、7,12-二甲基苯并[a]蒽、乙基亚硝基脲（ENU）和4-硝基喹啉1-氧化物交配前接受处理的ICR亲代小鼠的后代中，观察到表型异常有大量且显著的增加，但呋喃糠酰胺处理后的增加不显著。诱导异常的主要类型有腭裂、侏儒症、眼睑未闭、尾巴异常和露脑畸形。侏儒症、眼睑未闭和尾巴异常是存活异常的主要类型，其遗传方式似乎是具有不同表达率或外显率的显性突变。对于精子和精原细胞，产前异常的发生率随X射线、氨基甲酸乙酯或ENU的处理剂量增加而升高。精原细胞对X射线和氨基甲酸乙酯的敏感性低于精子，而ENU通过精原细胞处理诱导出非常高的产前异常发生率。与之前关于X射线的研究不同，精原细胞暴露后，在0至216拉德的剂量范围内，异常有明显的、几乎呈线性的增加。对于卵母细胞的处理，X射线和氨基甲酸乙酯的剂量增加时，异常也有明显增加。精子、精原细胞和成熟卵母细胞导致产前异常的X射线加倍剂量分别为12拉德、27拉德和19拉德。这些值与普通小鼠突变的值相似。然而，每拉德产前异常的平均发生率（精子为1.2×10⁻⁴，精原细胞为6.6×10⁻⁵，成熟卵母细胞为9.1×10⁻⁵）以及每克1微克ENU的发生率（精原细胞为3.4×10⁻⁴）比小鼠普通突变的发生率高4至40倍，因为本研究对总体表型异常进行了评分。从表型异常研究中获得的信息对于评估辐射和化学物质的遗传风险很有价值，因为大多数人类遗传疾病表现出这种不规则和不确定的遗传方式，而且大多数诱导异常与人类中发现的异常相似。
