Evidence map›Paper›PMID 23076150›Full record

ArticleThe Journal of biological chemistry2012

Effects of 6-thioguanine and S6-methylthioguanine on transcription in vitro and in human cells.

Changjun You, Xiaoxia Dai, Bifeng Yuan, Yinsheng Wang

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 23% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
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  4. Review
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  7. Article
  8. Review
  9. Cytotoxic and mutagenic properties of minor-grooveThe Journal of biological chemistry · 2018
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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 1 institution in 1 country.

Changjun YouDepartment of Chemistry, University of California, Riverside, California 92521-0403, USA.
Xiaoxia Dai
Bifeng Yuan
Yinsheng Wang
University of California, Riverside · US

Funding

Chemistry and Biology of DNA CarboxyalkylationR01DK082779 · NIDDK · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI WANG, YINSHENG · 2009 to 2016
$3.0M
NIDDK NIH HHS R01 DK082779
6 · The paper itself

Abstract

Thiopurine drugs are extensively used as chemotherapeutic agents in clinical practice, even though there is concern about the risk of therapy-related cancers. It has been previously suggested that the cytotoxicity of thiopurine drugs involves their metabolic activation, the resultant generation of 6-thioguanine ((S)G) and S(6)-methylthioguanine (S(6)mG) in DNA, and the futile mismatch repair triggered by replication-induced (S)G:T and S(6)mG:T mispairs. Disruption of transcription is known to be one of the major consequences of DNA damage induced by many antiviral and antitumor agents; however, it remains undefined how (S)G and S(6)mG compromise the efficiency and fidelity of transcription. Using our recently developed competitive transcription and adduct bypass assay, herein we examined the impact of (S)G and S(6)mG on transcription in vitro and in human cells. Our results revealed that, when situated on the transcribed strand, S(6)mG exhibited both inhibitory and mutagenic effects during transcription mediated by single-subunit T7 RNA polymerase or multisubunit human RNA polymerase II in vitro and in human cells. Moreover, we found that the impact of S(6)mG on transcriptional efficiency and fidelity is modulated by the transcription-coupled nucleotide excision repair capacity. In contrast, (S)G did not considerably compromise the efficiency or fidelity of transcription, and it was a poor substrate for NER. We propose that S(6)mG might contribute, at least in part, to thiopurine-mediated cytotoxicity through inhibition of transcription and to potential therapy-related carcinogenesis via transcriptional mutagenesis.

Indexed as

Transcription, GeneticAntimetabolites, AntineoplasticChromatography, LiquidDNADNA DamageDNA-Directed RNA PolymerasesDNA RepairElectrophoresis, Polyacrylamide GelFibroblastsGuanineHEK293 CellsHumansIn Vitro TechniquesModels, ChemicalMutagenesisMutation6-methylthioguanineAntimetabolites, Antineoplasticbacteriophage T7 RNA polymeraseDNADNA-Directed RNA PolymerasesGuanineRNAThioguanineViral Proteins

Identifiers

PMID23076150
PMCPMC3510796
OpenAlexW1991113904

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.