Brassica vegetables increase and apiaceous vegetables decrease cytochrome P450 1A2 activity in humans: changes in caffeine metabolite ratios in response to controlled vegetable diets

Abstract

enzymes (2,3). Induction or inhibition of biotransformation enzymes,CYP1A2 metabolizes various environmental procarcinoenzymes that activate or detoxify numerous xenobiotics, is gens, such as heterocyclic amines (4), nitrosamines (5) and one mechanism by which vegetables may alter cancer risk.aflatoxin B 1 (6). In humans, CYP1A2 activity, as measured by Using a randomized crossover design, we examined the caffeine metabolite ratios, is increased by cigarette smoke effect of various vegetable diets on cytochrome P450 (CYP) (7,8), cruciferous vegetables (9,10) and well-cooked meat (11). 1A2, N-acetyltransferase 2 (NAT2) and xanthine oxidaseCertain drugs and a few dietary constituents (12-14) have activity in humans. Men and women, non-smokers, on no been associated with reduced CYP1A2 activity in vivo. Genetic medication and 20-40 years of age ate four 6-day controlled polymorphisms in glutathione S-transferase (GST) have been diets: basal (vegetable-free) and basal with three botanically shown to associate with CYP1A2 activity, perhaps by modulatdefined vegetable groups. Enzyme activities were detering circulating levels of phytochemicals that induce this P450 mined by measuring urinary caffeine metabolite ratios enzyme (15,16). after a 200 mg caffeine dose on the last day of each feeding N-acetyltransferase 2 (NAT2) catalyzes acetylation of a period. Mean CYP1A2 activity for 19 men and 17 women variety of aromatic amines and hydrazines, including known (least squares means adjusted for sex, GSTM1 genotype, carcinogens. The NAT2 gene is polymorphic; point mutations urine volume and feeding period) with basal, brassica, in both coding and non-coding regions can result in decreased allium and apiaceous vegetable diets differed significantly expression, low activity or enzyme instability (17,18). Rapid (P ഛ ഛ 0.0005) by diet, irrespective of the caffeine metabolite and slow NAT2 phenotypes and the associated genotypes have molar ratio used to describe CYP1A2 activity; brassica been identified and both rapid and slow acetylation have been vegetables increased (P Ͻ0.04) and apiaceous vegetables associated with the risk of several cancers (19). Although decreased (P ഛ ഛ 0.02) activity compared with the basal and NAT2 is believed to be predominantly under genetic control, allium diets. There was no effect of diet on NAT2 and wide ranges exist in enzyme activity and associations have xanthine oxidase activities and none of the subjects differed been identified between NAT2 activity and some exposures, by GSTM1 genotype. These results demonstrate that while such as use of gout medication and intake of heavily browned one vegetable subgroup induces human CYP1A2 activity, fish (17). To date, controlled dietary interventions have not another subgroup inhibits it. This points to a complex found any effects of vegetables (9) or well-cooked meat (11) association between consumption of a typical diet of various vegetables and biotransformation enzyme activities in on NAT2 activity. humans, an association that may be difficult to...

Correlation of Cytochrome P450 (CYP) 1A2 Activity Using Caffeine Phenotyping and Olanzapine Disposition in Healthy Volunteers

“…Previous studies used urine samples collected from 4 to 5 h (Chung et al, 2000;Lampe et al, 2000;Sinues et al, 1999) or 0 to 24 h (Bertilsson et al, 1994;Sinues et al, 1999) after caffeine intake to assess CYP1A2 activity. We collected urine from 0 to 8 h in this study to minimize the effects of urine flow rate on excretion of different metabolites and also to make the sample collection easier.…”

Glucosinolates inBrassicavegetables: The influence of the food supply chain on intake, bioavailability and human health

“…Studies in humans have demonstrated that Brassica vegetables consumption can increase GST levels and activity in addition to GSH levels in lymphocytes. Brassica vegetables (radish, cauliflower, broccoli and cabbage) have been demonstrated to induce GSTl activity in peripheral lymphocytes [230]. In addition, in response to Brussels sprouts, levels of GSTa and GSTp were increased in plasma and in rectal cells, respectively [235,236].…”

Diet and cancer prevention

“…Potential mechanisms for cancer prevention include modulation of DNA methylation (Duthie, 1999), prevention of DNA adduct formation (Ames et al, 1995), induction of phase II carcinogen-metabolizing enzymes (Lampe, 1999;Lampe et al, 2000), alteration of hormone levels (Aldecruetz, 2002), and inhibition of nitrosamine formation and carcinogenbinding (Steinmetz and Potter, 1991b). Results from over 250 epidemiologic studies of fruits and vegetables and cancer have been summarized in several large reviews (Steinmetz and Potter, 1991a;Block et al, 1992;World Cancer Research Fund & American Institute for Cancer Research, 1997).…”