Effects of vitamin A on cyclophosphamide mutagenicity in vitro (Ames test) and in vivo (mouse micronucleus test).
The effect of vitamin A on cyclophosphamide mutagenicity was measured both in vitro and in vivo. In the Ames test in Salmonella typhimurium TA1535 with mouse-liver S-9 mix, the addition of retinol, retinyl acetate or retinyl palmitate caused a dose-dependent inhibition of cyclophosphamide mutagenicity. In the micronucleus test in male NMRI mice fed low, normal or high levels of vitamin A, the induction of micronuclei in bone marrow by an ip dose of cyclophosphamide was unaffected by vitamin A status. Thus, this study provides no evidence that activation of a procarcinogen in the liver or bone marrow of mice can be modified by vitamin A. One of the possible reasons for the observed absence of inhibition by vitamin A in vivo may be a lack of correlation between the oral dose of retinoid and the resulting level of vitamin A in the bone marrow. The difference between results in vitro and in vivo may also have been due to a difference in the availability and potency of added vitamin A in vitro compared with the forms absorbed and stored in vivo.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000648:ultrastructure; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors*; D004224:Diterpenes; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000037:antagonists & inhibitors*; D000084562:Retinyl Esters; D012486:Salmonella typhimurium / Q000235:genetics; D014801:Vitamin A / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*
D004224:Diterpenes; D009153:Mutagens; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; C009166:retinol acetate; D003520:Cyclophosphamide