Genomic instability in liver cells caused by an LPS-induced bystander-like effect
Authors: Olga Kovalchuk
James Thomas
Igor Kovalchuk
Paul Walz
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Bacterial infection; carcinogenesis; molecular mechanisms; heat-killed E. coli O157:H7; gene expression
Affiliations: Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada. 

Abstract:  Bacterial infection has been linked to carcinogenesis, however, there is lack of knowledge of molecular mechanisms that associate infection with the development of cancer. We analyzed possible effects of the consumption of heat-killed E. coli O157:H7 cells or its cellular components, DNA, RNA, protein or lipopolysaccharides (LPS) on gene expression in naïve liver cells. Four week old mice were provided water supplemented with whole heat-killed bacteria or bacterial components for a two week period. One group of animals was sacrificed immediately, whereas another group was allowed to consume uncontaminated tap water for an additional two weeks, and liver samples were collected, post mortem. Liver cells responded to exposure of whole heat-killed bacteria and LPS with alteration in γH2AX levels and levels of proteins involved in proliferation, DNA methylation (MeCP2, DNMT1, DNMT3A and 3B) or DNA repair (APE1 and KU70) as well as with changes in the expression of genes involved in stress response, cell cycle control and bile acid biosynthesis. Other bacterial components analysed in this study did not lead to any significant changes in the tested molecular parameters. This study suggests that lipopolysaccharides are a major component of Gram-negative bacteria that induce molecular changes within naïve cells of the host. 

Retracted: No

PubPeer comments:
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 Something went wrong with some of the figures above during the PubPeer upgrade. Here is an illustration of the concerns in Figures 2 and 4. Boxes of the same color highlight panels that look very similar, but that display a different timepoint or experiment. ![file] , 
 And here is an attempt to illustrate the possible duplications between Western blot panels in this paper and another paper by the same group, i.e. Environmental and Molecular Mutagenesis 54:421-428 (2013), DOI 10.1002 em.21787. As mentioned above, the EMM paper was submitted 2 days earlier than the PLOS ONE paper. Both papers appear to be describing very similar experiments. ![file] All these concerns have been reported to the journal in July 2014. , 
 Retracted [10 October 2022] . -------------- Following the publication of this article [1], concerns were raised regarding results presented in Figures 1, 2, 3, and 4. Specifically, - The following immunohistochemistry results appear similar: - - Figure 1A Control 4 Weeks and Figure 3A DNA 2 weeks when rotated 270u00b0. - - Figure 1A DNA 4 weeks, and Figure 3A DNA 4 week when rotated 270u00b0. - - Figure 1A LPS 2 weeks, and Figure 3A LPS 4 weeks when flipped along the vertical axis. - - Figure 1A LPS 4 weeks, and Figure 3A LPS 2 weeks when flipped along the vertical axis. - - Figure 1A Bacteria 4 weeks, and Figure 3A Bacteria 2 weeks when flipped along the horizontal axis and rotated 90u00b0. The following western blot results appear similar: - - Figure 4A Actin 4w lanes 1u201310, Figure 4B DNMT3A 4w lanes 1u201310, Figure 4D MeCP2 4w lanes 1u201310, and Figure 2A Actin 2w lanes 1u201310 when flipped along the vertical axis. - - Figure 2A Actin 4w lanes 11u201312 and Figure 4D MeCP2 4w lanes 11u201312 when flipped along the vertical axis. - - Figure 2A KU70 4w lanes 1u20134, Figure 2A KU70 4w lanes 5u20138, and Figure 4B Actin 2w lanes 5u20138 when flipped along the vertical axis. - - Figure 2B APE1 4w lanes 1u201312, Figure 2C Actin 4w lanes 1u201312, Figure 4B Actin 4w lanes 1u201312, and Figure 4C Actin lanes 1u201312. - - Figure 2B Actin 4w lanes 1u201312, Figure 2C Actin 2w lanes 1u201312 when rotated 180u00b0, and Figure 4D Actin 4w lanes 1u201312. - - Figure 2C PCNA 2w lanes 1u201312 and Figure 4A DNMT1 4w lanes 1u201312. - - Figure 4A Actin 4w lanes 11u201312 and Figure 4B DNMT3A 4w lanes 11u201312. The authors provided underlying data for the immunohistochemical results and the western blot data presented in this article, but these data did not resolve the concerns with the published figures. Following the discussion of these concerns with the authors, the corresponding author requested the retraction of this article. IK, JT, and OK agreed with the retraction and apologized for the issues with the published article, but stand by the articleu2019s findings. PW either did not respond directly or could not be reached. ,