PRELIMINARY-RESULTS OF ETHYLNITROSOUREA, ISOPROPYL METHANESULFONATE AND METHYL METHANESULFONATE ACTIVITY IN THE TESTIS AND EPIDIDYMAL SPERMATOZOA OF MUTA(TM) MICE

Male Muta(TM) Mice were given a single intraperitoneal dose of either 1/15 M phosphate buffer (pH 6) as the vehicle control, MMS 40 mg/kg, E NU 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 extract ed from whole testes and epididymal spermatozoa and analysed for mutat ion frequency. In the testes, no increase in mutation frequency was ob served, at either timepoint, for the animals treated with either MMS o r iPMS. A slight increase in the mutation frequency, above vehicle con trol values, was seen in the ENU-treated animals with a 3 day expressi on time. A 4-fold increase was observed in the ENU-treated animals exp osed for 63 days. In the epididymal spermatozoa, all of the test chemi cals 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 Ii-fold incr ease above control for MMS, ENU and iPMS, respectively. The Muta(TM) M ouse positive selection system appears to be sensitive to both the pre meiotic germ cell mutagen, ENU and postmeiotic germ cell mutagens, MMS and iPMS.