Modulation of Human Glutathione S-Transferases by Botanically Defined Vegetable Diets

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2000-08, Vol.9 (8), p.787-793
• Main Authors: LAMPE, J. W, CHU CHEN, SUE LI, PRUNTY, J, GRATE, M. T, MEEHAN, D. E, BARALE, K. V, DIGHTMAN, D. A, ZIDING FENG, POTTER, J. D
• Format: Article
• Language: English
• Subjects: Adult; Allium - metabolism; Anticarcinogenic Agents - metabolism; Apiaceae - metabolism; Biological and medical sciences; Biotransformation - genetics; Brassica - metabolism; Carcinogenesis, carcinogens and anticarcinogens; Cross-Over Studies; Female; Foods and miscellaneous; Glutathione Transferase - blood; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; Humans; Isoenzymes - blood; Isoenzymes - genetics; Isoenzymes - metabolism; Male; Medical sciences; Sex Factors; Statistics, Nonparametric; Tumors; Vegetables - metabolism
• ISSN: 1055-9965; 1538-7755

Glutathione S -transferases (GSTs) conjugate activated xenobiotics with glutathione; thus, GST induction may improve detoxification and excretion of potentially harmful compounds. Using a randomized cross-over design, we tested the hypothesis that, in humans, serum GST-α concentration (GST-α) and GST activity increase with vegetable consumption and that this effect is GSTM1 genotype dependent. Twenty-one men (10 GSTM1 -null and 11 GSTM1 +) and 22 women (15 GSTM1 -null and 7 GSTM1 +), nonsmokers, 20–40 years of age and not on medications, ate four 6-day controlled diets: basal (vegetable-free), and basal supplemented with three botanically defined groups of vegetables ( i.e., brassica, allium, and apiaceous). Fasting blood samples, collected on the last 2 days of each feeding period, were analyzed for GST-α, serum GST activity [against 1-chloro-2,4-dinitrobenzene (CDNB) and 7-chloro-4-nitrobenzo-2- oxa-1,3-diazole (NBD-Cl)] and peripheral-lymphocyte GST-μ activity (against trans -stilbene oxide). The brassica, but not allium or apiaceous, vegetable diets (relative to the basal diet) increased GST-α by 26% ( P = 0.005) and GST (NBD-Cl) activity by 7% ( P = 0.02) in the GSTM1 -null individuals, particularly the women. Apiaceous vegetable supplementation decreased GST-α in the GSTM1 + men ( P = 0.03). Among the GSTM1 + women, both brassica and the allium diets increased GST-μ activity by 18% ( P = 0.02) and 26% ( P = 0.001), respectively. The vegetable diets had no effect on GST (CDNB) activity, irrespective of GSTM1 genotype or sex. These results demonstrate that GSTM1 genotype has a significant effect on GST responses to diet and that brassica vegetables are most effective at inducing GST-α, whereas both brassica and allium vegetables induce GST-μ. GST responses were more pronounced in women than men, but it is not clear from this study whether this is a dose-per-body-weight or a sex-specific effect.