title: Effect of high sucrose diet on cytochrome P450 1A and heterocyclic amine mutagenesis.
abstract: To assess the effect of dietary sucrose on liver cytochrome P450 1A content and activity, male F344 rat weanlings were randomized into two diet groups for a period of 90 days. One group was fed a diet containing 65% of total calories from sucrose (HSD) while the other was fed standard lab chow (0% sucrose). Microsomal fractions from each of 10 animals in each group were used in Western immunoblot, mutagenesis and 7-alkoxyresorufin-0-deethylase (AROD) assays. No statistically significant difference in the mean quantity of liver CYP 1A2 was detected by Western blot analysis, while a significant decrease in mean liver CYP 1A1 was observed in the rats fed the HSD. Liver microsomal-dependent mutagenesis of two heterocyclic amines (HCAs), 2-amino-3,8-dimethyl-imadazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), in Salminella typhimurium TA98 was decreased in animals on the HSD compared to those on the control diet by 33% (p < 0.001) and 25% (p < 0.001), respectively. In addition, rats on the HSD had significantly decreased ethoxyresorufin-0-deethylase (EROD) and methoxyresorufin-0-deethylase (MROD) activity over a range of substrate concentrations. These results show that a HSD alters hepatic CYP 1A content and activity and suggests that the metabolism of substrates for this P450 subfamily may be significantly altered.
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: D000818:Animals; D002243:Carbolines / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004032:Diet; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009152:Mutagenicity Tests; D010088:Oxidoreductases / Q000378:metabolism; D011804:Quinolines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011810:Quinoxalines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013395:Sucrose / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D002243:Carbolines; D011804:Quinolines; D011810:Quinoxalines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D013395:Sucrose; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2