EVALUATION OF THE TRANSGENIC LAMBDA LACI MOUSE MODEL AS A SHORT-TERM PREDICTOR OF HERITABLE RISK/

Transgenic male C57BL/6 lambda/lacI mice were used to assess the mutag enic response in seminiferous tubules and epididymal spermatozoa 3 day s after exposure to ethylnitrosourea (ENU), iso-propyl methanesulfonat e (iPMS) and methyl methanesulfonate (MMS). No significant mutagenic r esponse was observed in epididymal spermatozoa for all three compounds , as expected 3 days after treatment. However, ENU and iPMS treated sa mples demonstrated significant mutagenic inductions relative to contro ls in seminiferous tubules while MMS treated samples did not. The fail ure of MMS to induce a mutagenic response in lambda/lacI transgenic mi ce is likely due to a combination of the low dose used, the short expr ession time after exposure and the reduced sensitivity to large deleti on events in transgenic lambda/lacI shuttle vectors. In addition, ex v ivo mutations were measured in control samples and iPMS treated sample s, where 33% of mutants from control samples and 35% of mutants from i PMS treated samples were mosaic.