Ehling U H, Neuhäuser-Klaus A
Institut für Säugetiergenetik, Gesellschaft für Strahlen- und Umweltforschung, Neuherberg, F.R.G.
Mutat Res. 1988 May;199(1):191-8. doi: 10.1016/0027-5107(88)90245-x.
Diethyl sulfate (DES), a monofunctional alkylating agent, induces mutations and chromosomal aberrations in many different organisms and cell systems, including dominant-lethal mutations in male mice. However, until now it could not be demonstrated that DES induces specific-locus mutations in mice. This observation would contradict the close correlation observed between the induction of dominant-lethal mutations and specific-locus mutations in mice with other chemicals. DES induces dominant-lethal and specific-locus mutations in spermatozoa and late spermatids of mice. The mutation frequency for dominant-lethal mutations is dose-dependent, while for specific-locus mutations it is independent of the dose. In the mating interval 5-8 days post-treatment the mutation frequency for 200 mg/kg DES is 17.0 X 10(-5) and for 300 mg/kg 7.5 X 10(-5) mutations per locus. The dose-dependent increase of dominant-lethal mutations probably reduced the chance of recovering specific-locus mutations. The importance of these findings for mutagenicity testing is discussed.
硫酸二乙酯（DES）是一种单功能烷基化剂，可在许多不同的生物体和细胞系统中诱发突变和染色体畸变，包括雄性小鼠中的显性致死突变。然而，到目前为止，尚未证实DES能诱发小鼠的特定基因座突变。这一观察结果与用其他化学物质处理小鼠时观察到的显性致死突变和特定基因座突变之间的密切相关性相矛盾。DES可在小鼠的精子和晚期精子细胞中诱发显性致死和特定基因座突变。显性致死突变的突变频率呈剂量依赖性，而特定基因座突变的频率与剂量无关。在处理后5 - 8天的交配间隔期，200 mg/kg DES的每个基因座突变频率为17.0×10⁻⁵，300 mg/kg为7.5×10⁻⁵。显性致死突变的剂量依赖性增加可能降低了恢复特定基因座突变的机会。文中讨论了这些发现对致突变性测试的重要性。
