Evaluation of experimental parameters in an S9 /human leukocyte SCE test with cyclophosphamide.
The experimental parameters S9 concentration, cofactor concentration and exposure time were investigated in a microsome test with human leukocyte cultures, To evaluate these parameters, their effects on cyclophosphamide-induced SCE frequencies and changes in cell proliferation were analyzed. By varying S9 concentration and exposure time, dose-effect relationships were found with respect to the induction of SCE. A relatively small effect was found when the concentrations of the cofactors NADP and G-6-P were varied. In general, an increase in SCE frequencies was accompanied by delayed cell proliferation. The importance of varying the experimental parameters to avoid false- negative results in microsome tests is discussed.
D000818:Animals; D002455:Cell Division; D003434:Crossing Over, Genetic; D003520:Cyclophosphamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005069:Evaluation Studies as Topic; D005958:Glucosephosphates / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000648:ultrastructure*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens; D009249:NADP / Q000378:metabolism; D051381:Rats; D012854:Sister Chromatid Exchange
D005958:Glucosephosphates; D009153:Mutagens; D009249:NADP; D003520:Cyclophosphamide