<i>CYP1A2, GSTM1</i>, and <i>GSTT1</i> Polymorphisms and Diet Effects on CYP1A2 Activity in a Crossover Feeding Trial

Peterson, Steven W.; Schwarz, Yvonne; Li, Shuying S.; Li, Lin; King, Irena B.; Chen, Chu; Eaton, David L.; Potter, John D.; Lampe, Johanna W.

doi:10.1158/1055-9965.epi-09-0589

Cited by 51 publications

(31 citation statements)

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“…A previous study in humans indicates that the change in activity of CYP enzymes achievable with dietary intervention is in the range of 14 – 24% [38]. Consumption of furanocoumarin containing foods and concomitant decrease in CYP1A2 activity may lead to a shift in the balance between activation and conjugation that might favor more complete conjugation and excretion of potential carcinogens.…”

Section: Discussionmentioning

confidence: 99%

Effects of Furanocoumarins from Apiaceous Vegetables on the Catalytic Activity of Recombinant Human Cytochrome P-450 1A2

et al. 2011

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Inhibition of cytochrome P-450 1A2 (CYP1A2)-mediated activation of procarcinogens may be an important chemopreventive mechanism. Consumption of apiaceous vegetables (rich in furanocoumarins) inhibits CYP1A2 in humans. Because many furanocoumarins are potent inhibitors of several CYP, we characterized the effects of three furanocoumarins from apiaceous vegetables on human CYP1A2 (hCYP1A2). We assessed hCYP1A2 methoxyresorufin O-demethylase (MROD) activity using microsomes from Saccharomyces cerevisiae expressing hCYP1A2. Isopimpinellin exhibited mechanism-based inactivation (MBI) of hCYP1A2 (Ki = 1.2 μM, kinact = 0.34 min−1, and partition ratio = 8). Imperatorin and trioxsalen were characterized as mixed inhibitors with Ki values of 0.007 and 0.10 μM, respectively. These results indicate that even if present at low levels in apiaceous vegetables, imperatorin, trioxsalen and isopimpinellin may contribute significantly to CYP1A2 inhibition and potentially decreased procarcinogen activation. Moreover, the in vivo effect of isopimpinellin on CYP1A2 may be longer lasting compared to reversible inhibitors.

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Section: Discussionmentioning

confidence: 99%

Effects of Furanocoumarins from Apiaceous Vegetables on the Catalytic Activity of Recombinant Human Cytochrome P-450 1A2

et al. 2011

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“…In terms of statistical analyses, focusing on one botanical group of vegetables, Cruciferae , may not reflect one's overall diet, as we consume vegetables and other foods in combinations. Even within vegetables, consumption of cruciferous vegetables was shown to increase CYP1A2 activity, which is associated with increased detoxification, in a feeding trial of healthy adults . In contrast, consumption of apiaceous vegetables such as carrots was shown to inhibit the enzyme activity in this trial.…”

Section: Observational Studies Of Cruciferous Vegetable or Itc Intakementioning

confidence: 61%

The Role of Cruciferous Vegetables and Isothiocyanates for Lung Cancer Prevention: Current Status, Challenges, and Future Research Directions

Zhang

Bergan

Shannon

et al. 2018

Molecular Nutrition Food Res

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Lung cancer remains a leading cause of cancer-related deaths in the United States. Although smoking and air pollution exposure are primary risk factors of lung cancer, diet has also been reported to contribute to lung cancer risk. Cruciferous vegetables contain many bioactive compounds that alter the detoxification process of air-borne carcinogenic compounds and, thereby, may decrease lung cancer risk. In the meta-analysis of 31 observational studies, cruciferous vegetable intake is inversely associated with lung cancer risk (summary odds ratio/relative risk = 0.81 and 95% confidence interval = 0.74-0.89 for comparing the highest with lowest intake categories). More observational studies need to measure urinary isothiocyanate (ITC) concentrations and investigate their association with lung cancer risk in populations with relatively high intake of cruciferous vegetables. Current evidence is limited to two phase 2 clinical trials with incomplete reporting. Hence, more short-term clinical phase 2 trials need to examine effects of various amounts and types of cruciferous vegetables on biomarkers of risk and efficacy before a large phase 3 trial can be conducted to assess effects upon lung cancer risk. This would help further elucidate whether the inverse association observed with self-reported cruciferous vegetable intake is indeed due to ITC content or other bioactive compounds.

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“…; Peterson et al. ). Results from this study show that I3C, an important indole in cruciferous vegetables, induces expression of CYP1A2 in several cellular systems, suggesting that this dietary component contributes to the higher CYP1A2 activity associated with the consumption of cruciferous vegetables.…”

Section: Discussionmentioning

confidence: 99%

“…Using a randomized, cross‐over feeding trial in humans, dose effects of cruciferous vegetables were investigated (Peterson et al. ). Compared with basal diet, basal plus single dose of cruciferous diet increased CYP1A2 activity and basal plus double dose of cruciferous diet resulted in further increases, with men experiencing greater dose‐response than women.…”

Section: Introductionmentioning

confidence: 99%

In vitro analysis of factors influencingCYP1A2expression as potential determinants of interindividual variation

Xie

Pogribna

Word

et al. 2017

Pharmacol Res Perspect

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Individual differences in drug metabolism contribute to interindividual variation that characterizes responses to drugs and risk in exposure to foreign chemicals. Large individual differences are found in expression levels of CYP1A2, a major drug‐metabolizing enzyme. Underlying causes for this variation are not well understood. Several factors, including tobacco smoking, consumption of cruciferous vegetables, and sex, have been associated with modulating CYP1A2 expression. To understand factors regulating expression of CYP1A2 in establishing a causal relationship, this study examined effects of cigarette smoke condensate (CSC), indole‐3‐carbinol (I3C), and 17β‐estradiol (estradiol) on CYP1A2 expression in in vitro systems using human liver and lung cells. Treatment with CSC (2–25 μg/mL) significantly increased levels of CYP1A2 in six cell lines examined, in a concentration‐ and time‐dependent manner. Fold changes in expression levels relative to controls varied among cell lines. CYP1A2 enzymatic activity also increased with CSC exposure. Treatment of H1299 and HepB3 cells with dietary agent I3C (50 and 100 μmol/L) increased CYP1A2 expression. In human cell lines H1299 and H1395, treatment with estradiol (10 and 100 nmol/L) significantly reduced expression of CYP1A2. Using ChIP assays, effects of CSC on histone modifications were analyzed. Increases in H3K4me3 and H4K16ac were observed at several segments in the CYP1A2 gene, whereas H3K27me3 decreased, following CSC treatment. These results suggest that CYP1A2 expression is affected epigenetically by CSC. Additional studies will be needed to further establish regulatory mechanisms underlying effects of various environmental, dietary, and endogenous factors on CYP1A2 expression in better predicting individual variation.

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CYP1A2, GSTM1, and GSTT1 Polymorphisms and Diet Effects on CYP1A2 Activity in a Crossover Feeding Trial

Cited by 51 publications

References 50 publications

Effects of Furanocoumarins from Apiaceous Vegetables on the Catalytic Activity of Recombinant Human Cytochrome P-450 1A2

Effects of Furanocoumarins from Apiaceous Vegetables on the Catalytic Activity of Recombinant Human Cytochrome P-450 1A2

The Role of Cruciferous Vegetables and Isothiocyanates for Lung Cancer Prevention: Current Status, Challenges, and Future Research Directions

In vitro analysis of factors influencingCYP1A2expression as potential determinants of interindividual variation

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