ArticleToxicology letters2012
Exposure to benzo[a]pyrene of Hepatic Cytochrome P450 Reductase Null (HRN) and P450 Reductase Conditional Null (RCN) mice: Detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and 32P-postlabelling.
Article in Toxicology letters, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Dietary cauliflower (Brassica oleracea var. botrytis) mitigates benzo[a]pyrene-induced oxidative stress, immune dysfunction, and tissue damage in Nile tilapia.Scientific reports · 2026Article
- A fast and reliable method for monitoring genomic instability in the model organism Caenorhabditis elegans.Archives of toxicology · 2021Article
- Benzo[International journal of molecular sciences · 2021Article
- Benzo[a]pyrene and Caenorhabditis elegans: defining the genotoxic potential in an organism lacking the classical CYP1A1 pathway.Archives of toxicology · 2021Article
- Enhanced DNA adduct formation by benzo[a]pyrene in human liver cells lacking cytochrome P450 oxidoreductase.Mutation research. Genetic toxicology and environmental mutagenesis · 2020Article
- Application of hepatic cytochrome bToxicology and applied pharmacology · 2019Article
- The role of cytochrome P450 enzymes in carcinogen activation and detoxication: an in vivo-in vitro paradox.Carcinogenesis · 2018Review
- Article
- Cytochrome bArchives of toxicology · 2018Article
- Altered gene expression profiles in the lungs of benzo[a]pyrene-exposed mice in the presence of lipopolysaccharide-induced pulmonary inflammation.Toxicology and applied pharmacology · 2017Article
- Impact of genetic modulation of SULT1A enzymes on DNA adduct formation by aristolochic acids and 3-nitrobenzanthrone.Archives of toxicology · 2017Article
- Comparison of human cytochrome P450 1A1-catalysed oxidation of benzo[Monatshefte fur chemie · 2017Article
- NADH:Cytochrome b5 Reductase and Cytochrome b5 Can Act as Sole Electron Donors to Human Cytochrome P450 1A1-Mediated Oxidation and DNA Adduct Formation by Benzo[a]pyrene.Chemical research in toxicology · 2016Article
- The impact of p53 on DNA damage and metabolic activation of the environmental carcinogen benzo[a]pyrene: effects in Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice.Archives of toxicology · 2016Article
- Pulmonary Inflammation Impacts on CYP1A1-Mediated Respiratory Tract DNA Damage Induced by the Carcinogenic Air Pollutant Benzo[a]pyrene.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- Polycyclic aromatic hydrocarbons: from metabolism to lung cancer.Toxicological sciences : an official journal of the Society of Toxicology · 2015Review
- TP53 mutations induced by BPDE in Xpa-WT and Xpa-Null human TP53 knock-in (Hupki) mouse embryo fibroblasts.Mutation research · 2015Article
- The anticancer drug ellipticine activated with cytochrome P450 mediates DNA damage determining its pharmacological efficiencies: studies with rats, Hepatic Cytochrome P450 Reductase Null (HRN™) mice and pure enzymes.International journal of molecular sciences · 2014Review
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- Article
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Benzo[a]pyrene (BaP) is a widespread environmental carcinogen activated by cytochrome P450 (P450) enzymes. In Hepatic P450 Reductase Null (HRN) and Reductase Conditional Null (RCN) mice, P450 oxidoreductase (Por) is deleted specifically in hepatocytes, resulting in the loss of essentially all hepatic P450 function. Treatment of HRN mice with a single i.p. or oral dose of BaP (12.5 or 125mg/kg body weight) resulted in higher DNA adduct levels in liver (up to 10-fold) than in wild-type (WT) mice, indicating that hepatic P450s appear to be more important for BaP detoxification in vivo. Similar results were obtained in RCN mice. We tested whether differences between hepatocytes and non-hepatocytes in P450 activity may underlie the increased liver BaP-DNA binding in HRN mice. Cellular localisation by immunohistochemistry of BaP-DNA adducts showed that HRN mice have ample capacity for formation of BaP-DNA adducts in liver, indicating that the metabolic process does not result in the generation of a reactive species different from that formed in WT mice. However, increased protein expression of cytochrome b(5) in hepatic microsomes of HRN relative to WT mice suggests that cytochrome b(5) may modulate the P450-mediated bioactivation of BaP in HRN mice, partially substituting the function of Por.
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