Evidence map›Paper›PMID 20443565›Full record

ArticleJournal of the American Chemical Society2010

Transcription inhibition by platinum-DNA cross-links in live mammalian cells.

Wee Han Ang, MyatNoeZin Myint, Stephen J Lippard

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

32 citing papers in PubMed, 95 citations in OpenAlex.

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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

3 authors at 1 institution in 1 country.

Wee Han AngDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
MyatNoeZin Myint
Stephen J Lippard
Massachusetts Institute of Technology · US

Funding

CHEMISTRY AND BIOLOGY OF PLATINUM ANTICANCER DRUGSR37CA034992 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LIPPARD, STEPHEN J. · 1990 to 2008
$5.7M
PATHOBIOLOGY OF B16 MELANOMA METASTASISR01CA032134 · NCI · NEW YORK MEDICAL COLLEGE · PI STACKPOLE, CHRISTOPHER W · 1985 to 1988
–
NCI NIH HHS CA032134NCI NIH HHS R37 CA034992
6 · The paper itself

Abstract

We have investigated the processing of site-specific Pt-DNA cross-links in live mammalian cells to enhance our understanding of the mechanism of action of platinum-based anticancer drugs. The activity of platinum drugs against cancer is mediated by a combination of processes including cell entry, drug activation, DNA-binding, and transcription inhibition. These drugs bind nuclear DNA to form Pt-DNA cross-links, which arrest key cellular functions, including transcription, and trigger a variety of responses, such as repair. Mechanistic investigations into the processing of specific Pt-DNA cross-links are critical for understanding the effects of platinum-DNA damage, but conventional in vitro techniques do not adequately account for the complex and intricate environment within a live cell. With this limitation in mind, we developed a strategy to study platinum cross-links on plasmid DNAs transfected into live mammalian cells based on luciferase reporter vectors containing defined platinum-DNA lesions that are either globally or site-specifically incorporated. Using cells with either competent or deficient nucleotide excision repair systems, we demonstrate that Pt-DNA cross-links impede transcription by blocking passage of the RNA polymerase complex and that nucleotide excision repair can remove the block and restore transcription. Results are presented for approximately 3800-base pair plasmids that are either globally platinated or carry a single 1,2-d(GpG) or 1,3-d(GpTpG) intrastrand cross-link formed by either cis-{Pt(NH(3))(2)}(2+) or cis-{Pt(R,R-dach)}(2+), where {Pt(NH(3))(2)}(2+) is the platinum unit conveyed by cisplatin and carboplatin and R,R-dach is the oxaliplatin ligand, R,R-1,2-diaminocyclohexane.

Indexed as

Antineoplastic AgentsBase SequenceCarboplatinCell Line, TumorCisplatinCross-Linking ReagentsDNADNA AdductsDNA DamageDNA-Directed RNA PolymerasesDNA RepairGenes, ReporterHumansOrganoplatinum CompoundsOxaliplatinPlasmidsAntineoplastic AgentsCarboplatinCisplatinCross-Linking ReagentsDNADNA AdductsDNA-Directed RNA PolymerasesOrganoplatinum CompoundsOxaliplatinPlatinumtransplatin

Identifiers

PMID20443565
PMCPMC2877768
OpenAlexW2156441552

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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.