Evidence map›Paper›PMID 19341467›Full record

ArticleBMC biotechnology2009

PhiC31 integrase induces a DNA damage response and chromosomal rearrangements in human adult fibroblasts.

Jian Liu, Tina Skjørringe, Torben Gjetting, Thomas G Jensen

Open access · goldAbstract read
In one paragraph

Article in BMC biotechnology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

20 citing papers in PubMed, 48 citations in OpenAlex.

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  17. Generation of induced pluripotent stem cells using site-specific integration with phage integrase.Proceedings of the National Academy of Sciences of the United States of America · 2010
    Article
  18. Biosafety assessment of site-directed transgene integration in human umbilical cord-lining cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2010
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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 3 institutions in 1 country.

Jian LiuThe Kennedy Center, Gl. Landevej 7, 2600 Glostrup, Denmark. jian.liu@med.lu.se
Tina Skjørringe
Torben Gjetting
Thomas G Jensen
Kennedy Center · DKAarhus University · DKRigshospitalet · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPhiC31 integrase facilitates efficient integration of transgenes into human and mouse genomes and is considered for clinical gene therapy. However recent studies have shown that the enzyme can induce various chromosomal abnormalities in primary human embryonic cells and mammalian cell lines. The mechanisms involved are unknown, but it has been proposed that PhiC31 attachment sites in the host genome recombine leading to chromosomal translocations.

resultsWe have studied possible effects of the PhiC31 integrase expression in human adult fibroblasts by karyotyping. All control cells were cytogenetically normal, whereas cells expressing PhiC31 integrase show chromosomal abnormalities confirming our previous results using primary embryonic fibroblasts. In order to study the early mechanisms involved we measured H2AX phosphorylation - a primary event in the response to DNA double-strand-breaks. Transient transfection with PhiC31 integrase encoding plasmids lead to an elevated number of cells positive for H2AX phosphorylation detected by immunofluorescence. Western blot analysis confirmed the upregulated H2AX phosphorylation, whereas markers for apoptosis as well as p53 and p21 were not induced. Cells transfected with plasmids encoding the Sleeping Beauty transposase remained cytogenetically normal, and in these cells less upregulation of H2AX phosphorylation could be detected.

conclusionIn primary human fibroblasts expression of PhiC31 integrase leads to a DNA damage response and chromosomal aberrations.

Indexed as

Chromosome AberrationsDNA DamageGenetic VectorsGene Transfer TechniquesCell LineFibroblastsHistonesHumansIntegrasesKaryotypingPhosphorylationPlasmidsTransfectionH2AX protein, humanHistonesIntegrases

Identifiers

PMID19341467
PMCPMC2682486
OpenAlexW1968692719

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Registered trials

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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.