Induction of DNA Damage in Mouse Colorectum by Administration of Colibactin-producing , Isolated from a Patient With Colorectal Cancer.

Background/aim: Among colorectal cancer-associated intestinal microbiota, colibactin-producing (clb) bacteria are attracting attention. We aimed to clarify the interaction between clb Escherichia coli and normal colorectal epithelial cells in vivo and in vitro.

Materials And Methods: Five-week-old female Balb/c mice were divided in an untreated group, a group treated with clb E. coli isolated from a Japanese patient with colorectal cancer (E. coli-50), and a group treated with non colibactin-producing E. coli (E. coli-50/ΔclbP). Mice were sacrificed at 18 weeks of treatment.

Results: Treatment with clb E. coli increased positivity for H2A histone family member X phosphorylated at Ser-139 (γH2AX) in epithelial cells of the luminal surface of the mouse rectum but this did not occur in the E. coli-50/ΔclbP and untreated groups. In an in vitro setting, the ratio of apoptotic cells was increased and cell counts were reduced by treatment with clb E. coli more than in untreated cells and normal rat colorectal epithelial cells.

Conclusion: E. coli-50 induced DNA damage in the mouse rectum, possibly by direct interaction between clb E. coli and normal colorectal epithelial cells. Our findings imply that regulation of clb E. coli infection may be a useful strategy for colorectal cancer control.