Takumi Narita1,2, Yuta Tsunematsu3, Noriyuki Miyoshi4, Masami Komiya2, Takahiro Hamoya1,2, Gen Fujii5, Yuko Yoshikawa6, Michio Sato3, Masanobu Kawanishi7, Haruhiko Sugimura8, Yuji Iwashita8, Yukari Totsuka9, Masaru Terasaki10, Kenji Watanabe3, Keiji Wakabayashi11, Michihiro Mutoh12,2. 1. Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. 2. Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan. 3. Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. 4. School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan. 5. Central Radioisotope Division, National Cancer Center Research Institute, Tokyo, Japan. 6. School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino, Japan. 7. Graduate School of Science and Radiation Research Center, Osaka Prefecture University, Sakai, Japan. 8. Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan. 9. Laboratory of Environmental Toxicology and Carcinogenesis, School of Pharmacy, Nihon University, Funabashi, Japan. 10. School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa, Japan. 11. Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan. 12. Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; mimutoh@koto.kpu-m.ac.jp.
Abstract
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.
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.
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