ArticleChemical research in toxicology2014
Role of hepatic and intestinal p450 enzymes in the metabolic activation of the colon carcinogen azoxymethane in mice.
Article in Chemical research in toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 63 citations in OpenAlex.
- Modeling ETBF-Mediated Colorectal Tumorigenesis Using AOM/DSS in Wild-Type Mice.International journal of molecular sciences · 2025Article
- Characterization of hepatic pathology during azoxymethane-induced acute liver failure.World journal of gastroenterology · 2025Article
- Mediterranean diet improves liver health but does not protect against azoxymethane-induced colon tumorigenesis compared to Western diet in A/J mice.Experimental and molecular pathology · 2025Article
- Article
- An intestinal TNature immunology · 2024Article
- Studies on the mechanism of local and extra-intestinal tissue manifestations in AOM-DSS-induced carcinogenesis in BALB/c mice: role of PARP-1, NLRP3, and autophagy.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Reconstructed human intestinal comet assay, a possible alternative in vitro model for genotoxicity assessment.Mutagenesis · 2023Article
- Review
- Ficus dubia latex extract prevent DMH-induced rat early colorectal carcinogenesis through the regulation of xenobiotic metabolism, inflammation, cell proliferation and apoptosis.Scientific reports · 2022Article
- Caffeine and Chlorogenic Acid Combination Attenuate Early-Stage Chemically Induced Colon Carcinogenesis in Mice: Involvement of oncomiR miR-21a-5p.International journal of molecular sciences · 2022Article
- Assessment of the Anti-Cancer Efficiency of Silver Moringa oleifera Leaves Nano-extract against Colon Cancer Induced Chemically in Rats.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet.Metabolites · 2021Article
- 2021 ISHEN guidelines on animal models of hepatic encephalopathy.Liver international : official journal of the International Association for the Study of the Liver · 2021Review
- Effect of mesenchymal stem cells on cytochrome-c release and inflammation in colon cancer induced by 1,2-dimethylhydrazine in Wistar albino rats.Bioscience reports · 2021Article
- Evaluation of the Biological Efficiency of Silver Nanoparticles Biosynthesized Using Croton tiglium L. Seeds Extract against Azoxymethane Induced Colon Cancer in Rats.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Effects of high-fat diet and intestinal aryl hydrocarbon receptor deletion on colon carcinogenesis.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Switching to a Healthy Diet Prevents the Detrimental Effects of Western Diet in a Colitis-Associated Colorectal Cancer Model.Nutrients · 2019Article
- Mapping insoluble indole metabolites in the gastrointestinal environment of a murine colorectal cancer model using desorption/ionisation on porous silicon imaging.Scientific reports · 2019Article
- Targeted Metabolomics Identifies the Cytochrome P450 Monooxygenase Eicosanoid Pathway as a Novel Therapeutic Target of Colon Tumorigenesis.Cancer research · 2019Article
- Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
P450-mediated bioactivation of azoxymethane (AOM), a colon carcinogen, leads to the formation of DNA adducts, of which O(6)-methylguanine (O(6)-mG) is the most mutagenic and contributes to colon tumorigenesis. To determine whether P450 enzymes of the liver and intestine both contribute to AOM bioactivation in vivo, we compared tissue levels of AOM-induced DNA adducts, microsomal AOM metabolic activities, and incidences of colonic aberrant crypt foci (ACF) among wild-type (WT), liver-specific P450 reductase (Cpr)-null (LCN), and intestinal epithelium-specific Cpr-null (IECN) mice. At 6 h following AOM treatment (at 14 mg/kg, s.c.), O(6)-mG and N(7)-mG levels were highest in the liver, followed by the colon, and then small intestine in WT mice. As expected, hepatic adduct levels were significantly lower (by >60%) in LCN mice but unchanged in IECN mice, whereas small-intestinal adduct levels were unchanged or increased in LCN mice but lower (by >50%) in IECN mice compared to that in WT mice. However, colonic adduct levels were unchanged in IECN mice compared to that in WT mice and increased in LCN mice (by 1.5-2.9-fold). The tissue-specific impact of the CPR loss in IECN and LCN mice on microsomal AOM metabolic activity was confirmed by rates of formation of formaldehyde and N(7)-mG in vitro. Furthermore, the incidence of ACF, a lesion preceding colon cancer, was similar in the three mouse strains. Thus, AOM-induced colonic DNA damage and ACF formation is not solely dependent on either hepatic or intestinal microsomal P450 enzymes. P450 enzymes in both the liver and intestine likely contribute to AOM-induced colon carcinogenesis.
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