title: Cruciferous vegetable feeding alters UGT1A1 activity: diet- and genotype-dependent changes in serum bilirubin in a controlled feeding trial.
abstract: 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.
authors.affiliation: Bastyr University, Kenmore, WA, USA.
authors.forename: Sandi L
authors.initials: SL
authors.lastname: Navarro
authors.forename: Sabrina
authors.initials: S
authors.lastname: Peterson
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.forename: Karen W
authors.initials: KW
authors.lastname: Makar
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Schwarz
authors.forename: Irena B
authors.initials: IB
authors.lastname: King
authors.forename: Shuying S
authors.initials: SS
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Mark
authors.initials: M
authors.lastname: Kestin
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Lampe