Dominant lethal mutations induced in mouse spermatogonia by antineoplastic drugs

Male mice were treated with nitrogen mustard (2.25 mg/kg), procarbazine (100 mg/kg) or vincristine (0.67 mg/kg). 5 weeks later they were mated to untreated females and the dominant lethal mutant rate was determined in the offspring by an in vitro analysis. Nitrogen mustard and procarbazine induced dominant lethal mutations to significant levels. Mutations were expressed, throughout early development, especially as a failure to form a trophectoderm outgrowth and to differentiate and proliferate an inner cell mass. Variations in the dominant lethal mutant rate were found from one week to the next, suggesting that differentiated and stem cell spermatogonia have differential sensitivity to mutation induction and cell killing by each drug.