EVALUATION OF SPONTANEOUS AND CHEMICAL-INDUCED LACI MUTATIONS IN GERM-CELLS FROM LAMBDA LACI TRANSGENIC MICE/

The spontaneous mutant frequency in germ cells isolated from seminifer ous tubules of two lambda/lacI transgenic mouse strains, C57BL/6 and B 6C3F(1) was evaluated. At least 500000 phage were screened for mutatio n at lacI for each animal using standardized assay procedures. The ger m cell spontaneous lacI mutant frequency was 17.8+/-8.1x10(-6) in C57B L/6 mice and 17.0+/-10.0x10(-6) in B6C3F(1) mice. The induction of ger m cell mutations by three well characterized alkylating agents were al so evaluated in C57BL/6 mice on day 3 after a single dose administrati on. The lacI mutant frequencies were significantly elevated in transge nic mice dosed with ENU at 150 mg/kg (2-fold increase above control) a nd 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 stu dies using the lambda/lacI transgenic system may be capable of detecti ng germ mutations induced by chemicals characterized either by point m utations or small, intragenic deletions but not those characterized by a predominance of multi-locus deletions.