Mattison J D, Penrose L B, Burlinson B
Glaxo Wellcome Research and Development, Ware, Hertfordshire, UK.
Mutat Res. 1997 Feb 14;388(2-3):123-7. doi: 10.1016/s1383-5718(96)00108-8.
Male Muta Mice were given a single intraperitoneal dose of either 1/15 M phosphate buffer (pH 6) as the vehicle control, MMS 40 mg/kg, ENU 150 mg/kg or iPMS 200 mg/kg, at a dose volume of 20 ml/kg. Animals from each group were killed 3 or 63 days after dosing, the DNA extracted from whole testes and epididymal spermatozoa and analysed for mutation frequency. In the testes, no increase in mutation frequency was observed, at either timepoint, for the animals treated with either MMS or iPMS. A slight increase in the mutation frequency, above vehicle control values, was seen in the ENU-treated animals with a 3 day expression time. A 4-fold increase was observed in the ENU-treated animals exposed for 63 days. In the epididymal spermatozoa, all of the test chemicals induced increases in mutation frequency, at both timepoints, with the exception of a negative result for MMS after 3 days. ENU induced a 2.5 and iPMS a induced a 4-fold increase above the control mutation frequency after 3 days. For all treatments, the later sampling time of 63 days gave an approximate 2-fold increase above the results of the 3-day timepoint. These increases amounted to a 2, 4.5 and 11-fold increase above control for MMS, ENU and iPMS, respectively. The Muta Mouse positive selection system appears to be sensitive to both the premeiotic germ cell mutagen, ENU and postmeiotic germ cell mutagens, MMS and iPMS.
给雄性突变小鼠腹腔注射单剂量的以下物质,剂量体积为20 ml/kg:作为溶剂对照的1/15 M磷酸盐缓冲液(pH 6)、40 mg/kg的甲基磺酸甲酯(MMS)、150 mg/kg的N-乙基-N-亚硝基脲(ENU)或200 mg/kg的异丙基甲烷磺酸酯(iPMS)。给药后3天或63天处死每组动物,从整个睾丸和附睾精子中提取DNA,并分析突变频率。在睾丸中,无论哪个时间点,用MMS或iPMS处理的动物的突变频率均未增加。在ENU处理的动物中,表达时间为3天时,突变频率比溶剂对照值略有增加。暴露63天的ENU处理动物中观察到突变频率增加了4倍。在附睾精子中,除3天后MMS的阴性结果外,所有受试化学物质在两个时间点均诱导突变频率增加。3天后,ENU诱导的突变频率比对照增加了2.5倍,iPMS诱导的突变频率比对照增加了4倍。对于所有处理,63天的后期采样时间比3天时间点的结果增加了约2倍。这些增加分别相当于MMS、ENU和iPMS比对照增加了2倍、4.5倍和11倍。突变小鼠阳性选择系统似乎对减数分裂前生殖细胞诱变剂ENU以及减数分裂后生殖细胞诱变剂MMS和iPMS均敏感。