ArticleInternational journal of cancer2016
Metabolic activation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine and DNA adduct formation depends on p53: Studies in Trp53(+/+),Trp53(+/-) and Trp53(-/-) mice.
Article in International journal of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Synthesizing Genotoxicity Results in the MultiFlow Assay With Point-of-Departure Analysis and ToxPi Visualization Techniques.Environmental and molecular mutagenesis · 2025Article
- Tissue Organoid Cultures Metabolize Dietary Carcinogens Proficiently and Are Effective Models for DNA Adduct Formation.Chemical research in toxicology · 2024Article
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Article
- Co-Exposure to Aristolochic Acids I and II Increases DNA Adduct Formation Responsible for Aristolochic Acid I-Mediated Carcinogenicity in Rats.International journal of molecular sciences · 2021Article
- Colon Cancer Risk of a Westernized Diet Is Reduced in Mice by Feeding Cruciferous or Apiaceous Vegetables at a Lower Dose of Carcinogen but Not a Higher Dose.Journal of cancer prevention · 2020Article
- Colon Transcriptomics Reveals Sex-Dependent Metabolic Signatures in Response to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Treatment in C57BL/6N Mice.International journal of molecular sciences · 2020Article
- Dietary phytochemicals as the potential protectors against carcinogenesis and their role in cancer chemoprevention.Clinical and experimental medicine · 2020Review
- The Impact of p53 on Aristolochic Acid I-Induced Gene Expression In Vivo.International journal of molecular sciences · 2019Article
- The impact of p53 on aristolochic acid I-induced nephrotoxicity and DNA damage in vivo and in vitro.Archives of toxicology · 2019Article
- Article
- Article
- Chemical Analysis of DNA Damage.Analytical chemistry · 2018Review
- Impact of genetic modulation of SULT1A enzymes on DNA adduct formation by aristolochic acids and 3-nitrobenzanthrone.Archives of toxicology · 2017Article
- γH2AX and p53 responses in TK6 cells discriminate promutagens and nongenotoxicants in the presence of rat liver S9.Environmental and molecular mutagenesis · 2016Article
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Authors and funding
9 authors at 6 institutions in 4 countries.
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Abstract
The expression of the tumor suppressor p53 can influence the bioactivation of, and DNA damage induced by, the environmental carcinogen benzo[a]pyrene, indicating a role for p53 in its cytochrome P450 (CYP)-mediated biotransformation. The carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which is formed during the cooking of food, is also metabolically activated by CYP enzymes, particularly CYP1A2. We investigated the potential role of p53 in PhIP metabolism in vivo by treating Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice with a single oral dose of 50 mg/kg body weight PhIP. N-(Deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP-C8-dG) levels in DNA, measured by liquid chromatography-tandem mass spectrometry, were significantly lower in liver, colon, forestomach and glandular stomach of Trp53(-/-) mice compared to Trp53(+/+) mice. Lower PhIP-DNA adduct levels in the livers of Trp53(-/-) mice correlated with lower Cyp1a2 enzyme activity (measured by methoxyresorufin-O-demethylase activity) in these animals. Interestingly, PhIP-DNA adduct levels were significantly higher in kidney and bladder of Trp53(-/-) mice compared to Trp53(+/+) mice, which was accompanied by higher sulfotransferase (Sult) 1a1 protein levels and increased Sult1a1 enzyme activity (measured by 2-naphthylsulfate formation from 2-naphthol) in kidneys of these animals. Our study demonstrates a role for p53 in the metabolism of PhIP in vivo, extending previous results on a novel role for p53 in xenobiotic metabolism. Our results also indicate that the impact of p53 on PhIP biotransformation is tissue-dependent and that in addition to Cyp1a enzymes, Sult1a1 can contribute to PhIP-DNA adduct formation.
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