| Compounds in fruits and vegetables have been shown to reduce cancer incidence by reducing oxidative stress and effecting phase I and II biotransformation enzymes. Activity of the phase II enzyme glutathione S-transferase (GST) pi is diminished in prostate cancer tissue, however, the carotenoid lycopene has been shown to increase GST's in tissues. Therefore, a feeding study examining the effect of lycopene on the regulation of GST and on biomarkers of oxidative stress including the GSH:GSSG ratio and lipid peroxidation by-product malondialdehyde (MDA) was conducted. Mice were fed 0-4,000 mg/kg lycopene over a period of 7 d. Due to the minute tissue size available from the mice a new selective and sensitive analysis method was developed using Ultra High Pressure Liquid Chromatography coupled with tandem mass spectrometry to quantify lycopene concentrations in prostate tissue. Although lycopene was found in prostate tissue, no changes occurred in GST activity from mice fed lycopene compared to control animals. In contrast, beneficial changes in oxidative markers occurred; GSH:GSSG ratios increased and MDA concentration decreased. The data show that a possible role lycopene plays in prostate cancer prevention is through its ability to reduce oxidative stress in prostate tissue.; Phase I and II enzyme systems are also influenced by macro and micronutrients in the diet. Consequently the influence of rodent diet (e.g. commercial chow verses purified diet) on the biotransformation pathways following flavone challenge was investigated. Mice and rats fed less refined diets (i.e. commercial chow) had higher levels of background expression of biotransformation enzymes. Following challenge with flavone for 3 days, animals fed an amino acid based purified diet had the largest increase in phase I and II activity and expression compared to animals on an egg white based diet and chow diet. These findings draw attention to the importance of background diet when making statements regarding the influence of phytochemicals, such as flavonoids, on the induction of biotransformation enzymes. |
