MUTATION ASSAYS IN MALE GERM-CELLS FROM TRANSGENIC MICE - OVERVIEW OFSTUDY AND CONCLUSIONS

Three confirmed mouse germ cell mutagens, ethyl nitrosourea (ENU), iso propyl methanesulphonate (iPMS) and methyl methanesulphonate (MMS), ha ve been evaluated for their activity as mutagens to the germ cell DNA of two strains of transgenic mice (lac I, Big Blue(TM) and LacZ, Muta( TM)Mouse), Both testicular DNA and epididymal sperm DNA were evaluated . A range of sampling times was studied, from 3 days post-dosing to 10 0 days post-dosing. ENU and iPMS were mutagenic to both testicular DNA and epididymal sperm DNA. Mutant frequencies were higher for both che micals in DNA recovered from testicular tissue than in epididymal sper m DNA. Likewise, mutant frequencies were higher for both DNA samples a t the later sampling times. MMS was not mutagenic under any condition of test. A good level of qualitative agreement in test results was see n for the two assays and for the same assays conducted in different la boratories, The level of quantitative agreement was not as high, but w as, nonetheless, generally good. Recommendations for the future conduc t of transgenic rodent germ cell mutation assays are made. The test da ta are discussed within the context of the larger question of how such assays should be integrated into the chemical hazard assessment proce ss.