Metabolism, covalent binding, and mutagenicity of aflatoxin B1 by liver extracts from rats of various ages.
The ability of S-9 fractions isolated from the livers of 4-, 12-, and 26-month-old male inbred F344 rats to activate and metabolize the hepatocarcinogen aflatoxin B1 [(AFB1) CAS: 1162-65-8] was studied. The following observations were made: The activation of AFB1 to compounds that are mutagenic in the Ames Salmonella-microsome test and to compounds that covalently bind DNA in vitro was similar for liver S-9 from 4- and 12-month-old rats. A 30-50% decrease in the activation of AFB1 occurred in rats between 12 and 26 months of age. The in vitro metabolism of AFB1 to chloroform-soluble and water-soluble metabolites was similar for 4- and 12-month-old rats and decreased significantly in rats after 12 months of age. The proportion of most of the chloroform-soluble metabolites of AFB1 formed by liver S-9 from 4-, 12-, and 26-month-old rats was similar. However, the proportion of aflatoxicol (CAS: 29611-03-8) produced by liver S-9 increased approximately twofold in rats between 12 and 26 months of age. The cytochrome P450 content and the NADPH cytochrome c reductase activity of liver microsomes decreased 40-45% in rats between 12 and 26 months of age. However, the activities of UDPglucuronyltransferases and most forms of glutathione S-transferase did not change significantly with increasing age in liver microsomes and cytosol, respectively.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism* / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D000348:Aflatoxins; D009153:Mutagens; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D009251:NADPH-Ferrihemoprotein Reductase; D014453:Glucuronosyltransferase