Apiaceous vegetable consumption decreases PhIP-induced DNA adducts and increases methylated PhIP metabolites in the urine metabolome in rats

Jae Kyeom Kim, Daniel D. Gallaher, Chi Chen, Dan Yao, Sabrina P. Trudo

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background: Heterocyclic aromatic amines, such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), are carcinogenic compounds produced during heating of protein-containing foods. Apiaceous vegetables inhibit PhIPactivating enzymes, whereas cruciferous vegetables induce both PhIP-activating and -detoxifying enzymes. Objective: We investigated the effects of these vegetables, either alone or combined, on PhIP metabolism and colonic DNA adduct formation in rats. Methods: Male Wistar rats were fed cruciferous vegetables (21%, wt:wt), apiaceous vegetables (21%, wt:wt), or a combination of both vegetables (10.5% wt:wt of each). Negative and positive control groups were fed an AIN-93G diet. After 6 d, all groups received an intraperitoneal injection of PhIP (10 mg · kg body weight-1) except for the negative control group, which received only vehicle. Urine was collected for 24 h after the injection for LC-tandem mass spectrometry metabolomic analyses. On day 7, rats were killed and tissues processed. Results: Compared with the positive control, cruciferous vegetables increased the activity of hepatic PhIP-activating enzymes [39.5% and 45.1% for cytochrome P450 (CYP) 1A1 (P = 0.0006) and CYP1A2 (P < 0.0001), respectively] and of uridine 5'- diphospho-glucuronosyltransferase 1A (PhIP-detoxifying) by 24.5% (P = 0.0267). Apiaceous vegetables did not inhibit PhIPactivating enzymes, yet reduced colonic PhIP-DNA adducts by 20.4% (P = 0.0496). Metabolomic analyses indicated that apiaceous vegetables increased the relative abundance of urinary methylated PhIP metabolites. The sum of these methylated metabolites inversely correlated with colonic PhIP-DNA adducts (r = -0.43, P = 0.01).We detected a novel methylated urinary PhIP metabolite and demonstrated that methylated metabolites are produced in the human liver S9 fraction. Conclusions: Apiaceous vegetables did not inhibit the activity of PhIP-activating enzymes in rats, suggesting that the reduction in PhIP-DNA adducts may involve other pathways. Further investigation of the importance of PhIP methylation in carcinogen metabolism is warranted, given the inverse correlation of methylated PhIP metabolites with a biomarker of carcinogenesis and the detection of a novel methylated PhIP metabolite.

Original languageEnglish (US)
Pages (from-to)442-451
Number of pages10
JournalJournal of Nutrition
Issue number3
StatePublished - 2015

Bibliographical note

Publisher Copyright:
© 2015 American Society for Nutrition.


  • 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
  • Apiaceous vegetables
  • Biotransformation enzymes
  • Cruciferous vegetables
  • DNA adducts
  • Heterocyclic aromatic amines
  • Metabolomics
  • N-methyltransferase


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