Comparison of dominant lethal and heritable translocation methodologies.
Groups of male Alderly Park mice of proven fertility were dosed by gavage for 5 consecutive days per week for 8 weeks or 5 consecutive days only with 100 or 150 mg/kg body weight ethyl methanesulphonate (EMS) or by intraperitoneal injection once a week for 8 weeks or once only with 500 mg/kg shikimic acid. Animals dosed in this manner were compared in the dominant lethal and heritable translocation assays. Animals were mated for 2 consecutive weeks following the 8-week treatment and for 8 consecutive weeks after the 1-week treatment: regimes which were thus non-specific and specific respectively for the stages of spermatogenesis. An additional method of measuring dominant lethality involving counting uterine scars after weaning (Soares (1972) Mutation Res., 16, 425-427) was used and also compared with the conventional method. EMS was clearly confirmed as a mutagen but this was not the case for shikimic acid. For screening purposes the dominant lethal 8-week mating assay was much more efficient in return for the same effort for detecting mutagenic responses than an 8-week mating heritable translocation assay, since the induction of dominant lethal effects paralleled the induction of heritable translocations. 8-week treatment with EMS showed increased dominant lethality but severely reduced fertility and the small numbers of male offspring born made potential heritable effects difficult to assess. The 1-week treatment with EMS produced both dominant lethal and heritable effects. Soares' method can be useful for determining dominant lethal effects in a heritable translocation assay. The "sieving" method of mating to determine partial and total sterility questions the necessity for a negative control in a heritable translocation study.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D005799:Genes, Dominant; D005804:Genes, Lethal; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens; D012765:Shikimic Acid / Q000494:pharmacology; D014178:Translocation, Genetic
D009153:Mutagens; D012765:Shikimic Acid; D005020:Ethyl Methanesulfonate