Germ-cell mutagenesis in lambda lacZ transgenic mice treated with ethylating and methylating agents: comparison with specific-locus test.

Germ-cell mutagenesis has been studied in male lambda lacZ transgenic mice in such a way that the data can be compared with literature data for germ-cell mutagenesis obtained with the specific-locus test (SLT). Mutagenesis induced by ethylnitrosourea (ENU), ethylmethanesulphonate (EMS), methylnitrosourea (MNU) and methylmethanesulphonate (MMS), has been studied in mature spermatozoa isolated from the epididymis and vas deferens. In order to investigate mutagenesis in different phases of spermatogenesis, animals were sacrificed at various time points after treatment. ENU at 150 mg/kg body weight significantly induced mutations in stem cells (analysis at 100 days post-treatment), but not in post-stem cells (7 days post-treatment). EMS (250 mg/kg) and MMS (60 mg/kg) induced mutations only in post-stem cells (7 days), but not in stem cells (100 days). MNU (70 mg/kg) resulted in an increase of mutations in both post-stem cells (14 and 37 days) and stem cells (100 days), although the latter, due to a limited number of data, was not statistically significant. All these data are in accordance with published SLT data. These results indicate that lambda lacZ transgenic mice are a suitable model to study gene mutations in different phases of spermatogenesis.