EFFECT OF ETHYLNITROSOUREA AND METHYL METHANESULFONATE ON MUTATION FREQUENCY IN MUTA(TM)MOUSE GERM-CELLS (SEMINIFEROUS TUBULE CELLS AND EPIDIDYMIS SPERMATOZOA)

As part of the Germ Cell Collaborative Study, we used the positive-sel ection Muta(TM) Mouse model to evaluate the effects of two direct alky lating agents, ethylnitrosourea (ENU) and methyl methanesulfonate (MMS ), on male germ cells. The LacZ mutation frequency in seminiferous tub ule cells and epididymis spermatozoa was measured 3, 14, 25 and 50 day s after a single intraperitoneal (i.p.) administration of 150 mg/kg EN U and 3 and 14 days after a single i.p. administration of 40 mg/kg MMS . Three and 14 days after ENU treatment, the mutation frequency was sl ightly but significantly increased in seminiferous tubule cells (3.5- and 3.6-fold, respectively), while it remained unchanged in epididymis spermatozoa. After 25 and 50 days, time-dependent increase in the mut ation frequency was observed in seminiferous tubule cells (8.9- and 14 .3-fold, respectively) and epididymis spermatozoa (3.4- and 7.9-fold, respectively), confirming the sensitivity of premeiotic cells to the m utagenic activity of ENU. Three and 14 days after MMS administration, the mutation frequency remained unchanged in seminiferous tubule cells and epididymis spermatozoa. The inability of Muta(TM) Mouse model to reveal the mutagenic activity of MMS was confirmed in bone marrow cell s, 14 days after treatment. These data indicate that the Muta(TM) Mous e model can be used to detect the induction of gene mutations but not chromosome damage in germ cells.