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

  作者 Matsubara, S; Takasu, S; Tsukamoto, T; Mutoh, M; Masuda, S; Sugimura, T; Wakabayashi, K; Totsuka, Y  
  选自 期刊  International Journal of Cancer;  卷期  2012年130-2;  页码  259-266  
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[摘要]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 welland moderatelydifferentiated glandular stomach adenocarcinomas in the MGs at the incidence of 31% under H. pylori infection at 54104 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.

 
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