Evaluation of spontaneous and chemical-induced lacI mutations in germ cells from lambda/ lacI transgenic mice

Abstract

The spontaneous mutant frequency in germ cells isolated from seminiferous tubules of two lambda/ lacI transgenic mouse strains, C57BL/6 and B6C3F 1 was evaluated. At least 500 000 phage were screened for mutation at lacI for each animal using standardized assay procedures. The germ cell spontaneous lacI mutant frequency was 17.8±8.1×10 −6 in C57BL/6 mice and 17.0±10.0×10 −6 in B6C3F 1 mice. The induction of germ cell mutations by three well characterized alkylating agents were also evaluated in C57BL/6 mice on day 3 after a single dose administration. The lacI mutant frequencies were significantly elevated in transgenic mice dosed with ENU at 150 mg/kg (2-fold increase above control) and iPMS at 200 mg/kg (3-fold increase above control) but not in those receiving MMS at 40 mg/kg. These findings suggest that single dose studies using the lambda/ lacI transgenic system may be capable of detecting germ mutations induced by chemicals characterized either by point mutations or small, intragenic deletions but not those characterized by a predominance of multi-locus deletions.