Scope: 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. Methods and results: 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. Conclusion: 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.
Bibliographical noteFunding Information:
S.P.T. and D.D.G. designed the research; J.K.K., C.M.G., D.Y., D.D.G., and S.P.T. conducted the research; J.K.K., D.D.G., and C.C. analyzed the data; J.K.K. and S.P.T. drafted the manuscript; J.K.K., D.D.G., and S.P.T. had primary responsibility for the final content. All authors read and approved the final manuscript. This work was supported by Healthy Foods, Healthy Lives Institute, University of Minnesota (J.K.K.), NCI K07 CA128952 (S.P.T.), and the Analytical Biochemistry Shared Resource at the Masonic Cancer Center that is supported by NIH P30 CA077598. We would like to thank Dr. Robert Turesky for his expert guidance and resources.
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
- 2-Amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine
- DNA adducts
- Phenethyl isothiocyanate