title: Genomic instability in liver cells caused by an LPS-induced bystander-like effect.
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.
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada. igor.kovalchuk@uleth.ca
authors.forename: Igor
authors.initials: I
authors.lastname: Kovalchuk
authors.forename: Paul
authors.initials: P
authors.lastname: Walz
authors.forename: James
authors.initials: J
authors.lastname: Thomas
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D024201:Bystander Effect; D004249:DNA Damage; D019175:DNA Methylation; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D042822:Genomic Instability; D022781:Hepatocytes / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D000072200:Ku Autoantigen; D008070:Lipopolysaccharides / Q000502:physiology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D006657:Histones; D008070:Lipopolysaccharides; D018809:Proliferating Cell Nuclear Antigen; C475961:gamma-H2AX protein, mouse; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase