Induction of specific-locus and dominant lethal mutations in male mice by ifosfamide (Holoxan)

Ifosfamide induced dominant lethal mutations in spermatozoa of mice at dose s of 200 and 300 mg/kg and in spermatids and spermatocytes at 600 mg/kg. Th e highest dose also induced specific-locus mutations in post-spermatogonial germ-cell stages of mice but not in spermatogonial stem cells. The nature of the induced mutations suggests they are intergenic. The spermatogenic sp ecificity of ifosfamide in mouse germ cells is similar to that of the struc turally related cytostatic drugs cyclophosphamide and trofosfamide. Due to the post-spermatogonial germ cell specificity of ifosfamide, the genetic ri sk is limited to a few weeks after exposure.