Evidence map›Paper›PMID 25173884›Full record

ArticleCarcinogenesis2014

Identification of cytochrome P450 enzymes critical for lung tumorigenesis by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): insights from a novel Cyp2abfgs-null mouse.

Lei Li, Vandana Megaraj, Yuan Wei, Xinxin Ding

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.3field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 32 citations in OpenAlex.

  1. Observational
  2. Article
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  8. Assessing cytochrome P450 function using genetically engineered mouse models.Advances in pharmacology (San Diego, Calif.) · 2022
    Review
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  10. Review
  11. Article
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  14. P450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2018
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Lei LiWadsworth Center, New York State Department of Health, Albany, NY 12201, USA, School of Public Health, State University of New York at Albany, Albany, NY 12201, USA and.
Vandana MegarajWadsworth Center, New York State Department of Health, Albany, NY 12201, USA, School of Public Health, State University of New York at Albany, Albany, NY 12201, USA and.
Yuan WeiWadsworth Center, New York State Department of Health, Albany, NY 12201, USA, School of Public Health, State University of New York at Albany, Albany, NY 12201, USA and.
Xinxin DingWadsworth Center, New York State Department of Health, Albany, NY 12201, USA, School of Public Health, State University of New York at Albany, Albany, NY 12201, USA and Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, NY 12203, USA xding@sunycnse.com.
University at Albany, State University of New York · USNew York State Department of Health · US

Funding

Human CYP2A and respiratory tract xenobiotic toxicityR01CA092596 · NCI · WADSWORTH CENTER · PI DING, XINXIN · 2003 to 2020
$6.1M
NCI NIH HHS CA092596
6 · The paper itself

Abstract

Cytochrome P450 (P450) enzymes encoded by the mouse Cyp2abfgs gene cluster are preferentially expressed in the respiratory tract. Previous studies have demonstrated that pulmonary P450-mediated bioactivation is necessary for lung tumorigenesis induced by the tobacco-specific lung procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and that CYP2A5 mediates a noteworthy fraction, but not all, of NNK bioactivation in the lung. The aim of this study was to determine whether other P450s encoded by the Cyp2abfgs gene cluster also play significant roles in NNK lung tumorigenesis. A novel Cyp2abfgs-null mouse was generated, in which all Cyp2a, 2b, 2g, 2f and 2s genes are deleted. The Cyp2abfgs-null mouse was viable, fertile and without discernible physiological abnormalities or compensatory increases in the expression of other P450s. NNK bioactivation in vitro and NNK-induced DNA adduction and lung tumorigenesis in vivo were determined for wild-type (WT) and Cyp2abfgs-null mice; the results were compared with previous findings from Cyp2a5-null mice. The Cyp2abfgs-null mice exhibited significantly lower rates of NNK bioactivation in lung and liver microsomes, compared with either WT or Cyp2a5-null mice. The levels of lung O(6)-methyl guanine DNA adduct were also substantially reduced in Cyp2abfgs-null mice, compared with either WT or Cyp2a5-null mice. Moreover, the Cyp2abfgs-null mice were largely resistant to NNK-induced lung tumorigenesis at both low (50mg/kg) and high (200mg/kg) NNK doses, in contrast to the WT or Cyp2a5-null mice. These results indicate for the first time that, collectively, the CYP2A, 2B, 2F, 2G, and 2S enzymes are indispensable for NNK-induced lung tumorigenesis.

Indexed as

CarcinogenesisAnimalsCarcinogensCytochrome P-450 Enzyme SystemDNA AdductsLung NeoplasmsMiceMicrosomes, LiverMultigene FamilyNicotianaNitrosamines4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanoneCarcinogensCytochrome P-450 Enzyme SystemDNA AdductsNitrosamines

Identifiers

PMID25173884
PMCPMC4216058
OpenAlexW2062942223

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.