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Mutagenesis vol. 11 no. 6 pp. 611-613, 1996
© 1996 UK Environmental Mutagen Society/Oxford University Press

research-article

Methyl methanesulphonate (MMS) as a resource conserving and reliable positive control agent for male rat and male mouse dominant lethal assays

J. Ashby1, P.A. Lefevre, B.M. Elliott and M.J.L. Clapp

Zeneca Central Toxicology Laboratory Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK

A single i.p. injection of methyl methanesulphonate (MMS; 40 mg/kg) to male rats, followed by their sequential mating over 4–28 days post-dosing, was shown to induce dominant lethal (DL) effects in two strains of rats and in four separate experiments. Activity was evident between 4 days postdosing (sampling treated spermatozoa) and 28 days postdosing (sampling treated early spermatids). The highest incidences of resorptions were seen between days 15 and 21 post-dosing, being {bsim}1 week later than the peak of activity in the mouse. The DL effects seen were strong and could be detected as early as 4–10 days post-dosing, at which time only small reductions in pregnancy rates and total implantation numbers were seen. Similar, but weaker, mutagenic effects have been reported by Ehling et al for MMS in mouse DL assays. These data indicate, therefore, that MMS provides a convenient positive control agent for both male rat and male mouse dominant lethal assays, requiring only approximately five treated males, each mated to two females at around 14 days post-dosing.

1To whom correspondence should be addressed


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