Effects of saturated and unsaturated dietary fat on aflatoxin B1 metabolism.
Male Fisher 344 rats were fed diets containing either 20% corn oil, 20% coconut oil or 18% coconut oil plus 2% corn oil for 3 wk. A single dose of [3H]aflatoxin B1 [(3H]AFB1) was administered ip and the biliary excretion of aflatoxin metabolites and the binding of 3H to nucleic acids were studied. In other experiments the in vitro metabolism of AFB1 by liver postmitochondrial supernatants prepared from rats fed the different sources of dietary fat was determined. The major nonextractable aqueous metabolite of AFB1 was the aflatoxin B1-glutathione conjugate (AFB1-GSH). Variation in the source of dietary fat did not affect production of the conjugate, nor was in vivo binding of AFB1 to nucleic acids affected. Aflatoxin P1 ( AFP1 )--mostly conjugated--and aflatoxin M1 (AFM1) were also identified in the bile, and the quantities of these metabolites produced were unaffected by the dietary treatments. The metabolites recovered in the in vitro study included aflatoxins Q1, P1 and M1. The corn oil diet produced a higher microsomal cytochrome P-450 level than the coconut oil diet. Associated with the higher level of cytochrome P-450 was increased in vitro conversion of AFB1 to AFQ1 and AFM1, but not to AFP1 . The in vitro production of aqueous metabolites and the covalent binding of metabolites to protein was unaffected by the dietary treatments. The results of the in vivo and in vitro studies suggest that the formation of the putative carcinogenic metabolite, AFB1-epoxide, which undergoes detoxification through glutathione conjugation, is not affected by the type of dietary fat. These observations further suggest that dietary fat, in particular unsaturated fat, affects AFB1 carcinogenesis through a mechanism other than by alteration of the metabolic activation of AFB1.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009696:Nucleic Acids / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D000348:Aflatoxins; D004041:Dietary Fats; D005231:Fatty Acids, Unsaturated; D009696:Nucleic Acids; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1