Induction of glandular stomach cancers in Helicobacter pylori-infected Mongolian gerbils by 1-nitrosoindole-3-acetonitrile

Authors

  • Satoshi Matsubara,

    1. Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
    2. Food Research Department, Yakult Central Institute for Microbiological Research, Kunitachi-shi, Tokyo, Japan
    Search for more papers by this author
  • Shinji Takasu,

    1. Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
    Search for more papers by this author
  • Tetsuya Tsukamoto,

    1. Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu-shi, Mie, Japan
    Search for more papers by this author
  • Michihiro Mutoh,

    1. Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
    Search for more papers by this author
  • Shuichi Masuda,

    1. Department of Food and Nutritional Sciences, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada, Shizuoka, Japan
    Search for more papers by this author
  • Takashi Sugimura,

    1. Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
    Search for more papers by this author
  • Keiji Wakabayashi,

    1. Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
    2. Department of Food and Nutritional Sciences, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada, Shizuoka, Japan
    Search for more papers by this author
  • Yukari Totsuka

    Corresponding author
    1. Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
    • Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan
    Search for more papers by this author
    • Tel.: +81-3-3542-2511, Fax: +81-3-3543-9305


Abstract

Helicobacter pylori (H. pylori) infection and high intake of various traditional salt-preserved foods are regarded as risk factors for human gastric cancer. We previously reported that Chinese cabbage contains indole compounds, such as indole-3-acetonitrile, a mutagen precursor. 1-Nitrosoindole-3-acetonitrile (NIAN), formed by the treatment of indole-3-acetonitrile with nitrite under acidic conditions, shows direct-acting mutagenicity. In the present study, NIAN administration by gavage to Mongolian gerbils (MGs) at the dose of 100 mg/kg two times a week resulted in three adduct spots (1.6 adducts/108 nucleotides in total), detected in DNA samples from the glandular stomach by 32P-postlabeling methods. Treatment with six consecutive doses of 100 mg/kg of NIAN, two times a week for 3 weeks, induced well—and moderately—differentiated glandular stomach adenocarcinomas in the MGs at the incidence of 31% under H. pylori infection at 54–104 weeks. Such lesions were not induced in MGs given broth alone, broth + NIAN or infection with H. pylori alone. Thus, endogenous carcinogens formed from nitrosation of indole compounds could be critical risk factors for human gastric cancer development under the influence of H. pylori infection.

Ancillary