Influence of mouse liver stored vitamin A on the induction of mutations (Ames tests) and SCE of bone marrow cells by aflatoxin B1, benzo(a)pyrene, or cyclophosphamide.
Male mice (C57BL/6J) at 2 weeks of age were divided into two groups and maintained on a vitamin A-deficient or vitamin A-(retinyl acetate) supplemented diet. After 8 weeks, the average liver vitamin A concentration of mice fed on vitamin A-deficient or -supplemented diet was 36 +/- 7 micrograms/g vs 287 +/- 22 micrograms/g, respectively. Uninduced liver S9 fractions were prepared from both groups of mice and used to activate (with cofactors) the precarcinogens aflatoxin B1 (AFB), cyclophosphamide (CPP), dimethylbenz(a)anthracene (DMBA), and benzo(a)pyrene (BP) in the Salmonella mutagenicity assay. S9 fraction prepared from both groups of mice failed to activate CPP to metabolites mutagenic in tester strains TA100 and TA1535 or to activate DMBA to metabolites mutagenic in TA100, but effectively activated AFB and BP to metabolites mutagenic in TA98. Comparison of activation activities of S9 prepared from liver of mice fed a high or low level of vitamin A was made with T98 treated with AFB or BP using three doses of S9 (50, 100, and 200 microliters/plate). S9 fractions from mice with a high liver vitamin A level were consistently less potent than S9 fractions from mice with a low liver vitamin A level in activating AFB to its mutagenic metabolites. This effect was not observed in BP-treated plates. Administration of AFB to groups of mice with a high liver vitamin A level induced significantly less SCE in bone marrow cells than did administration of AFB to mice with a low liver vitamin A level. This differential sensitivity was not observed when the two groups of mice were treated with either BP or CPP. The possible relationship between vitamin A levels in vivo and mutagenesis or carcinogenesis are discussed briefly.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D001711:Biotransformation / Q000187:drug effects; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003520:Cyclophosphamide / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009152:Mutagenicity Tests; D009154:Mutation; D012854:Sister Chromatid Exchange / Q000187:drug effects; D014801:Vitamin A / Q000378:metabolism / Q000502:physiology*; D014802:Vitamin A Deficiency / Q000378:metabolism
D000348:Aflatoxins; D002273:Carcinogens; D014801:Vitamin A; D001564:Benzo(a)pyrene; D003520:Cyclophosphamide; D016604:Aflatoxin B1