Characterization of water-soluble glucuronide and sulphate conjugates of aflatoxin B1. 1. Urinary excretion in monkey, rat and mouse.
Water-soluble aflatoxin conjugates prepared from urine samples from rats, mice and rhesus monkeys dosed with [14C]aflatoxin B1 (AFB1) ip or iv were hydrolysed by enzymes (beta-glucuronidase and sulphatase), acid or a combination of both treatments. Different amounts of AFB1 and its metabolites were found in hydrolysates from different sources, indicating the presence of glucuronide, sulphate and possibly mercapturate conjugates of aflatoxins. In addition to aflatoxins M1, P1, Q1 and B2a, AFB1 was frequently identified in the products released from the hydrolysates. These water-soluble aflatoxin conjugates were not mutagenic to Salmonella typhimurium TA98 in the presence of rat-liver S-9 mix. However, chloroform extracts of the hydrolysates from beta-glucuronidase and sulphatase treatment showed mutagenic activity in these bacteria in the presence of S-9 mix. Although very low levels of AFB1 radioactivity were detected in the hydrolysates, the potent mutagenic activity of AFB1 contributed to the high numbers of revertant colonies. AFP1 was detected in urine samples from monkeys that were pretreated with phenobarbital before an iv dose of AFB1. No mutagenic activity was detected in the enzymatic hydrolysate of the sample from these monkeys. The results thus indicate that AFB1 can form glucuronide and/or sulphate conjugate(s) directly and be excreted in the urine.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism* / Q000633:toxicity / Q000652:urine; D000818:Animals; D001345:Autoradiography; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005965:Glucuronates / Q000378:metabolism*; D007263:Infusions, Parenteral; D007274:Injections, Intraperitoneal; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D013045:Species Specificity; D013431:Sulfates / Q000378:metabolism*
D000348:Aflatoxins; D002250:Carbon Radioisotopes; D005965:Glucuronates; D013431:Sulfates; D016604:Aflatoxin B1; D010634:Phenobarbital