Evidence map›Paper›PMID 23335782›Full record

ArticleNucleic acids research2013

The nitrosated bile acid DNA lesion O6-carboxymethylguanine is a substrate for the human DNA repair protein O6-methylguanine-DNA methyltransferase.

Pattama Senthong, Christopher L Millington, Oliver J Wilkinson, Andrew S Marriott, Amanda J Watson, Onrapak Reamtong, Claire E Eyers, David M Williams, Geoffrey P Margison, Andrew C Povey

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

12 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Metabolic Activation and DNA Interactions of CarcinogenicInternational journal of molecular sciences · 2022
    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

10 authors at 3 institutions in 1 country.

Pattama SenthongCentre for Occupational and Environmental Health, Faculty of Medical & Human Sciences, University of Manchester, Manchester M13 9PL, UK.
Christopher L Millington
Oliver J Wilkinson
Andrew S Marriott
Amanda J Watson
Onrapak Reamtong
Claire E Eyers
David M Williams
Geoffrey P Margison
Andrew C Povey
University of Manchester · GBCancer Research UK Manchester Institute · GBUniversity of Sheffield · GB

Funding

Biotechnology and Biological Sciences Research CouncilCancer Research UK
6 · The paper itself

Abstract

The consumption of red meat is a risk factor in human colorectal cancer (CRC). One hypothesis is that red meat facilitates the nitrosation of bile acid conjugates and amino acids, which rapidly convert to DNA-damaging carcinogens. Indeed, the toxic and mutagenic DNA adduct O(6)-carboxymethylguanine (O(6)-CMG) is frequently present in human DNA, increases in abundance in people with high levels of dietary red meat and may therefore be a causative factor in CRC. Previous reports suggested that O(6)-CMG is not a substrate for the human version of the DNA damage reversal protein O(6)-methylguanine-DNA methyltransferase (MGMT), which protects against the genotoxic effects of other O(6)-alkylguanine lesions by removing alkyl groups from the O(6)-position. We now show that synthetic oligodeoxyribonucleotides containing the known MGMT substrate O(6)-methylguanine (O(6)-MeG) or O(6)-CMG effectively inactivate MGMT in vitro (IC50 0.93 and 1.8 nM, respectively). Inactivation involves the removal of the O(6)-alkyl group and its transfer to the active-site cysteine residue of MGMT. O(6)-CMG is therefore an MGMT substrate, and hence MGMT is likely to be a protective factor in CRC under conditions where O(6)-CMG is a potential causative agent.

Indexed as

Base SequenceBile Acids and SaltsCatalytic DomainColorectal NeoplasmsDNA AdductsDNA Modification MethylasesDNA Repair EnzymesEscherichia coli ProteinsGTP-Binding ProteinsGuanineHumansMembrane ProteinsMethyltransferasesMolecular WeightOligodeoxyribonucleotidesSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationATL1 protein, humanBile Acids and SaltsDNA AdductsDNA Modification MethylasesDNA Repair EnzymesEscherichia coli ProteinsGTP-Binding ProteinsGuanineMembrane ProteinsMethyltransferasesMGMT protein, humanOgt protein, E coliOligodeoxyribonucleotidesTumor Suppressor Proteins

Identifiers

PMID23335782
PMCPMC3597670
OpenAlexW2111357708

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.