title: Effect of high sucrose diet on liver enzyme content and activity and aflatoxin B1-induced mutagenesis.
abstract: Aflatoxin B1 (AFB1) is a fungal toxin and contaminant that has been implicated in human liver carcinogenesis. In this study we evaluated the effect of a 65% of total calories from sucrose diet (HSD) for 90 days on hepatic cytochrome P450 (CYP450) and glutathione-S-transferase (GST) activity compared to rats maintained on standard lab chow (0% sucrose). There was a statistically significant increase in the number of S. typhimurium His+ revertants (p < 0.001) generated from the incubation of AFB1 with hepatic microsomes from rats fed a HSD. The HSD did not affect the total microsomal CYP450 content nor content of CYP450 1A2, 2B1, 2 isoforms which activate AFB1. Alkoxyresorufin O-dealkylase activity (MROD, PROD) of microsomes from animals fed HSD was decreased by 73% and 49%, respectively. MROD activity is linked to CYP 1A2 activity while PROD is linked to CYP 2B1,2 activity. Although the amount of CYP 3A was significantly decreased in rats fed a HSD, its activity, determined by the presence of the fluorometric metabolite 7-hydroxyquinidine, was unchanged. GST activity was significantly lower in the rats fed HSD.
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: Leandra P
authors.initials: LP
authors.lastname: Peters
authors.forename: Robert W
authors.initials: RW
authors.lastname: Teel
mesh_terms: D016604:Aflatoxin B1 / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D019422:Dietary Sucrose / Q000008:administration & dosage*; D018565:Food-Drug Interactions; D005982:Glutathione Transferase / Q000378:metabolism; D007527:Isoenzymes; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D016296:Mutagenesis / Q000187:drug effects*; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
chemical_list: D019422:Dietary Sucrose; D007527:Isoenzymes; D009153:Mutagens; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D005982:Glutathione Transferase