The detection of gene mutation in the tubular sperm of Muta™Mice following a single intraperitoneal treatment with methyl methanesulphonate or ethylnitrosourea

Abstract

Transgenic mouse assays, such as Muta™Mouse, provide a method to predict the potential target organ carcinogenicity of chemical compounds. As part of a collaborative study, the effects of the direct-acting mutagens, methyl methanesulphonate (MMS) and ethylnitrosourea (ENU), were investigated for gene mutation in the tubular sperm of Muta™Mice testes after a single intraperitoneal exposure. Groups of male Muta™Mice were dosed intraperitoneally with either 1/15 M phosphate buffer, 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 tubular sperm DNA. The results showed a mean mutation frequency (MF) of 2.1×10 5 (64 mutants per 3.05×10 6 PFU) for the 10 vehicle-treated mice, a mean MF of 2.8×10 5 (78 mutants per 2.75×10 6 PFU) for the 10 MMS-treated mice and a mean MF of 9.1×10 5 (194 mutants per 2.14×10 6 PFU) for the 8 ENU-treated mice; this latter value representing a 4.5-fold increase over the vehicle control values.