Preliminary results of ethylnitrosourea, isopropyl methanesulphonate and methyl methanesulphonate activity in the testis and epididymal spermatozoa of Muta™Mice

Abstract

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.