Effect of high sucrose diet on cytochrome P450 1A and heterocyclic amine mutagenesis

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 1A2 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.