Heat-killed bacteria induce genome instability in mouse small intestine, liver and spleen tissues.
Bacterial infection has been associated with several malignancies, yet the exact mechanism of infection-associated carcinogenesis remains obscure. Furthermore, it is still not clear whether oncontransformation requires an active infection process, or merely the presence of inactivated bacteria remnants is enough to cause deleterious effects. Here, we analyzed whether or not consumption of non-pathogenic and pathogenic heat-killed Escherichia coli leads to changes in genome stability in somatic tissues of exposed animals. For one week, mice were given to drink filtered or not-filtered water contaminated with heat-killed non-pathogenic E. coli DH5alpha or heat-killed pathogenic E. coli O157:H7 Sakai. Control animals received tap water. One week after exposure, molecular changes were analyzed in the small intestine, an organ that is in immediate contact with contaminated water. Additionally, we studied the effect in the distant spleen and liver, the organs that are involved in an immune response and detoxification, respectively. Finally, muscles were chosen as neutral tissues that were not supposed to be affected. Intestinal, liver and spleen but not muscle cells responded to all bacterial treatments with an increased level of DNA damage monitored by the induction of gammaH2AX foci. In the intestine, elevated levels of DNA damage were in parallel with an increase in Ku70 and p53 expression. We have also found an elevated level of cellular proliferation in the intestine, liver and spleen but not in muscle tissues of all exposed animals as measured by increase in PCNA levels. Our data suggest that exposure to heat-killed filtered bacteria can trigger substantial molecular responses and cause genomic instability in target and distant organs. Even though bacteria were non-pathogenic and unable to cause infection, their remnants still caused a profound effect on exposed animals.
Koturbash
Igor
I
Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, Canada. igor.kovalchuk@uleth.ca
Thomas
James E
JE
Kovalchuk
Olga
O
Kovalchuk
Igor
I
D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry* / Q000472:pathogenicity; D019453:Escherichia coli O157 / Q000737:chemistry* / Q000472:pathogenicity; D042822:Genomic Instability; D006657:Histones / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism / Q000382:microbiology*; D000072200:Ku Autoantigen; D008099:Liver / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism / Q000382:microbiology; D013154:Spleen / Q000378:metabolism / Q000382:microbiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D006657:Histones; D016159:Tumor Suppressor Protein p53; C475961:gamma-H2AX protein, mouse; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen