Mutagenic activity of cyclophosphamide, trofosfamide, and ifosfamide in drosophila melanogaster. specific induction of recessive lethals in the absence of detectable chromosome breakage.

The mutagenicity of cyclophosphamide (EndoxanR), trofosfamide (IxotenR), and ifosfamide was tested on male germ cells, mainly mature sperm, of Drosophila melanogaster. The genetic end points used were sex-linked recessive lethals, dominant lethals, sex chromosome loss, and partial Y chromosome loss. For recessive sex-linked lethals, all three substances induced a significant increase over the control. The effectiveness was not concentration dependent. None of the compounds induced dominant lethals, or complete or partial loss of the sex chromosome. The results are interpreted to indicate the existence of a rate-limiting factor which acts as restriction on the amount of active metabolite in the target cell. This amount is considered to be lower than that required to cause a detectable increase in chromosome breakage types of damage, but is detectable with the higher resolving power of the recessive lethal test.