In vitro genotoxicity analyses of colibactin-producing E. coli isolated from a Japanese colorectal cancer patient

Masanobu Kawanishi; Yuuta Hisatomi; Yoshimitsu Oda; Chiaki Shimohara; Yuta Tsunematsu; Michio Sato; Yuichiro Hirayama; Noriyuki Miyoshi; Yuji Iwashita; Yuko Yoshikawa; Haruhiko Sugimura; Michihiro Mutoh; Hideki Ishikawa; Keiji Wakabayashi; Takashi Yagi; Kenji Watanabe

doi:10.2131/jts.44.871

Letter

In vitro genotoxicity analyses of colibactin-producing E. coli isolated from a Japanese colorectal cancer patient

Masanobu Kawanishi, Yuuta Hisatomi, Yoshimitsu Oda, Chiaki Shimohara, Yuta Tsunematsu, Michio Sato, Yuichiro Hirayama, Noriyuki Miyoshi, Yuji Iwashita, Yuko Yoshikawa, Haruhiko Sugimura, Michihiro Mutoh, Hideki Ishikawa, Keiji Wakabayashi, Takashi Yagi, Kenji Watanabe

Author information

Masanobu Kawanishi
Graduate School of Science and Radiation Research Center, Osaka Prefecture University
Yuuta Hisatomi
Graduate School of Science and Radiation Research Center, Osaka Prefecture University
Yoshimitsu Oda
Graduate School of Science and Radiation Research Center, Osaka Prefecture University
Chiaki Shimohara
Graduate School of Science and Radiation Research Center, Osaka Prefecture University
Yuta Tsunematsu
Department of Pharmaceutical Sciences, University of Shizuoka
Michio Sato
Department of Pharmaceutical Sciences, University of Shizuoka
Yuichiro Hirayama
Department of Pharmaceutical Sciences, University of Shizuoka
Noriyuki Miyoshi
Graduate School of Nutritional and Environmental Sciences, University of Shizuoka
Yuji Iwashita
Department of Tumor Pathology, Hamamatsu University School of Medicine
Yuko Yoshikawa
Graduate School of Nutritional and Environmental Sciences, University of Shizuoka
School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University
Haruhiko Sugimura
Department of Tumor Pathology, Hamamatsu University School of Medicine
Michihiro Mutoh
Division of Prevention, Center for Public Health Sciences, National Cancer Center
Hideki Ishikawa
Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine
Keiji Wakabayashi
Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka
Takashi Yagi
Graduate School of Science and Radiation Research Center, Osaka Prefecture University
Kenji Watanabe
Department of Pharmaceutical Sciences, University of Shizuoka

Keywords: Colibactin, Genotoxicity, DNA damage, Mammalian cells

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2019 Volume 44 Issue 12 Pages 871-876

DOI https://doi.org/10.2131/jts.44.871

Details

Abstract

Colibactin is a polyketide-peptide genotoxin produced by enteric bacteria such as E. coli, and is considered to contribute to the development of colorectal cancer. We previously isolated E. coli strains from Japanese colorectal cancer patients, and in the present study we investigated the genotoxic potency of the colibactin-producing (clb⁺) E. coli strains that carry the polyketide synthases “pks” gene cluster (pks⁺) and an isogenic clb^- mutant in which the colibactin-producing ability is impaired. Measurement of phosphorylated histone H2AX indicated that DNA double strand breaks were induced in mammalian CHO AA8 cells infected with the clb⁺ E. coli strains. Induction of DNA damage response (SOS response) by crude extract of the clb⁺ strains was 1.7 times higher than that of the clb^- E. coli in an umu assay with a Salmonella typhimurium TA1535/pSK1002 tester strain. Micronucleus test with CHO AA8 cells revealed that infection with the clb⁺ strains induced genotoxicity, i.e., the frequencies of micronucleated cells infected with clb⁺ strain were 4-6 times higher than with the clb^- strain. Since the intestinal flora are affected by dietary habits that are strongly associated with ethnicity, these data may contribute to both risk evaluation and prevention of colorectal cancer in the Japanese population.

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