The cytochrome P-450-dependent hydroxylation of T-2 toxin in various animal species.
Gas-liquid chromatography was used to investigate the hepatic and intestinal metabolism of T-2 toxin, a cytotoxic and immunodepressive trichothecene produced by species of Fusarium. The hepatic S-9 and microsomal fractions of various species hydroxylated T-2 toxin to form 3'-hydroxy-T-2. HT-2 toxin, a deacetylated metabolite of T-2 toxin formed by reactions involving microsomal esterases, was also hydroxylated, to 3'-hydroxy HT-2 toxin. Experiments with inhibitors and inducers of the cytochrome P-450-dependent system revealed that these two hydroxylation reactions were catalysed by the cytochrome P-450-dependent monooxygenase system. Species comparisons using rats, mice, guinea-pigs, rabbits, pigs, cows and chickens showed that the rate of the hydroxylation reaction was highest in the hepatic microsomes of guinea-pigs, followed by mice. Chickens possessed a low activity both in the hydrolysis and hydroxylation reactions. No hydroxylated metabolites were produced by the intestinal microsomes of rabbits. These two hydroxylated metabolites were far less cytotoxic to Reuber hepatoma cells than the parent compound, T-2 toxin.
D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D006168:Guinea Pigs; D006900:Hydroxylation; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000378:metabolism*; D013045:Species Specificity; D013552:Swine; D013605:T-2 Toxin / Q000378:metabolism* / Q000633:toxicity
D065607:Cytochrome P-450 Enzyme Inhibitors; D012717:Sesquiterpenes; D003577:Cytochrome P-450 Enzyme System; D013605:T-2 Toxin