Mutagenic activity of cyclophosphamide, ifosfamide, and trofosfamide in different genes of escherichia coli and salmonella typhimurium after biotransformation through extracts of rodent liver.

Abstract

Experiments are performed to compare the mutagenic properties of the three phosphamide esters of nitrogen mustard, cyclophosphamide (CP), ifosfamide (IF), and trofosfamide (TF), in different bacterial systems. The systems include forward mutations leading to resistance against 5-methyltryptophan (MTR) and from galR-s18 to gal-+ in Escherichia coli 343/113, back mutations from arg56 to arg-+ in Escherichia coli 343/113 and back mutations from hisG46 to his-+ in Salmonella typhimurium TA1535. CP, IF, and TF are not mutagenic per se. After biotransformation through isolated rodent liver homogenates (S-9 fraction) all three compounds exhibit mutagenic activity in the order CP smaller than IF smaller than TF. Specific activating potential of mouse liver extracts is higher than that of rat liver. Except for back mutations in S. typhimurium TA1535, all mutation systems tested show a similar pattern of induction after treatment with CP, IF, and TF. However, because gal-+ mutations are not induced by CP under conditions where arg-+ and MTR are induced, it is suggested that more than one mutational system be used in routine mutagenicity testing.