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Cruciferous Vegetable Feeding Alters UGT1A1 Activity: Diet- and Genotype-Dependent Changes in Serum Bilirubin in a Controlled Feeding Trial

leeallanchina 添加于 2010-1-5 02:10 | 2647 次阅读 | 0 个评论

作者
Navarro SL, Peterson S, Chen C, Makar KW, Schwarz Y, King IB, Li SS, Li L, Kestin M, Lampe JW
摘要
Chemoprevention by isothiocyanates from cruciferous vegetables occurs partly through up-regulation of phase II conjugating enzymes, such as UDP-glucuronosyltransferases (UGT). UGT1A1 glucuronidates bilirubin, estrogens, and several dietary carcinogens. The UGT1A1*28 polymorphism reduces transcription compared with the wild-type, resulting in decreased enzyme activity. Isothiocyanates are metabolized by glutathione S-transferases (GST); variants may alter isothiocyanate clearance such that response to crucifers may vary by genotype. We evaluated, in a randomized, controlled, crossover feeding trial in humans (n = 70), three test diets (single- and double-"dose" cruciferous and cruciferous plus apiaceous) compared with a fruit and vegetable–free basal diet. We measured serum bilirubin concentrations on days 0, 7, 11, and 14 of each 2-week feeding period to monitor UGT1A1 activity and determined effects of UGT1A1*28 and GSTM1/GSTT1-null variants on response. Aggregate bilirubin response to all vegetable-containing diets was statistically significantly lower compared with the basal diet (P < 0.03 for all). Within each UGT1A1 genotype, lower bilirubin concentrations were seen in *1/*1 in both single- and double-dose cruciferous diets compared with basal (P < 0.03 for both); *1/*28 in double-dose cruciferous and cruciferous plus apiaceous compared with basal, and cruciferous plus apiaceous compared with single-dose cruciferous (P < 0.02 for all); and *28/*28 in all vegetable-containing diets compared with basal (P < 0.02 for all). Evaluation of the effects of diet stratified by GST genotype revealed some statistically significant genotypic differences; however, the magnitude was similar and not statistically significant between genotypes. These results may have implications for altering carcinogen metabolism through dietary intervention, particularly among UGT1A1*28/*28 individuals.
详细资料
- 文献种类:期刊
- 期刊名称: Cancer Prevention Research
- 期刊缩写: Cancer Prevention Research
- 期卷页: 2009年第2卷第4期 345-352页
- ISBN: 1940-6207
标签

Isothiocyanates • cruciferous vegetables UDP-glucuronosyltransferase (UGT) 1A1 bilirubin glutathione S-transferase (GST) apiaceous sulforaphane
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十字花科蔬菜的保健作用古已有之，中药中的植物药值得开发，日常的蔬菜如西红柿，白菜都值得研究。