THE DETECTION OF GENE MUTATION IN THE TUBULAR SPERM OF MUTA(TM)MICE FOLLOWING A SINGLE INTRAPERITONEAL TREATMENT WITH METHYL METHANESULFONATE OR ETHYLNITROSOUREA

Transgenic mouse assays, such as Muta(TM) Mouse, provide a method to p redict the potential target organ carcinogenicity of chemical compound s. As part of a collaborative study, the effects of the direct-acting mutagens, methyl methanesulphonate (MMS) and ethylnitrosourea (ENU), w ere investigated for gene mutation in the tubular sperm of Muta(TM) Mi ce testes after a single intraperitoneal exposure. Groups of male Muta (TM) Mice were dosed intraperitoneally with either 1/15 M phosphate bu ffer, pH 6.0 (vehicle control), 40 mg/kg methyl methanesulphonate (MMS ) or 150 mg/kg ethylnitrosourea (ENU). The animals were sacrificed 14 days after the single dose. Mutation frequencies were determined in tu bular sperm DNA. The results showed a mean mutation frequency (MF) of 2.1x10(5) (64 mutants per 3.05x10(6) PFU) for the 10 vehicle-treated m ice, a mean MF of 2.8x10(5) (78 mutants per 2.75x10(6) PFU) for the 10 MMS-treated mice and a mean MF of 9.1x10(5) (194 mutants per 2.14x10( 6) PFU) for the 8 ENU-treated mice; this latter value representing a 4 .5-fold increase over the vehicle control values.