title: Phenethyl isothiocyanate and indole-3-carbinol from cruciferous vegetables, but not furanocoumarins from apiaceous vegetables, reduced PhIP-induced DNA adducts in Wistar rats.
abstract: We previously showed that apiaceous but not cruciferous vegetables reduced DNA adducts formed by 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) in rats. Here, we report the effects of the putative chemopreventive phytochemicals from these vegetables on PhIP metabolism and DNA adduct formation.
  
  
  
  Rats received three supplemented diets: P + I (phenethyl isothiocyanate and indole-3-carbinol), furanocoumarins (FC, 5-methoxypsoralen, 8-methoxypsoralen, and isopimpinellin), and combination (P + I and FC). Phytochemical supplementation matched the levels in vegetables fed in our previous study. After 6 days, rats were injected with PhIP (10 mg/kg body wt) and killed after 24-h urine collection. Compared to the control, P + I increased activity of hepatic cytochrome P450 (CYP) 1A1 (10.1-fold), CYP1A2 (3.62-fold), and sulfotransferase 1A1 (2.70-fold). The combination diet also increased CYP1A1 and CYP1A2 activity. Urinary metabolomics revealed that PhIP metabolite profiles generally agreed with biotransformation enzyme activities. P + I and combination diets reduced PhIP-DNA adducts by 43.5 and 24.1%, respectively, whereas FC had no effect on adducts, compared to the control diet.
  
  
  
  Effects of phytochemicals on metabolic outcomes and markers of carcinogenesis might differ from fresh vegetables, thus limiting the inferences that one can draw from the effects of purified phytochemicals on the health benefits of the vegetables from which they derive.
authors.affiliation: School of Human Environmental Sciences, University of Arkansas, Fayetteville, AR, USA.
authors.forename: Jae Kyeom
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Gallaher
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN, USA.
authors.forename: Chi
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN, USA.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Gallaher
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Yao
authors.affiliation: School of Human Environmental Sciences, University of Arkansas, Fayetteville, AR, USA. trudo@uark.edu.
authors.forename: Sabrina P
authors.initials: SP
authors.lastname: Trudo
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D015239:Arylsulfotransferase / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003106:Colon / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D018736:DNA Adducts / Q000187:drug effects*; D019587:Dietary Supplements; D011564:Furocoumarins / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism; D007093:Imidazoles / Q000633:toxicity / Q000652:urine; D007211:Indoles / Q000494:pharmacology*; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D017208:Rats, Wistar; D014675:Vegetables / Q000737:chemistry*; D000099148:UGT1A1 Enzyme
chemical_list: D016588:Anticarcinogenic Agents; D015239:Arylsulfotransferase; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D018736:DNA Adducts; D011564:Furocoumarins; D014453:Glucuronosyltransferase; D007093:Imidazoles; D007211:Indoles; D017879:Isothiocyanates; C499946:Ugt1a1 protein, rat; D000099148:UGT1A1 Enzyme; C058305:phenethyl isothiocyanate; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; C016517:indole-3-carbinol; C017170:Cyp1a2 protein, rat; C573795:Sult1a1 protein, rat
keywords: 2-Amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine; DNA adducts; Furanocoumarins; Indole-3-carbinol; Phenethyl isothiocyanate