Carcinogenesis, Vol. 20, No. 4, 669-676,
April 1999
© 1999 Oxford University Press
Helicobacter pylori infection enhances glandular stomach carcinogenesis in Mongolian gerbils treated with chemical carcinogens
1 Laboratory of Pathology, Aichi Cancer Center Research Institute, 1–1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464–8681,
2 Department of Gastrointestinal Surgery, Postgraduate School of Medicine, University of Tokyo, 3–28–6 Mejirodai, Bunkyou-ku, Tokyo 112–8688 and
3 First Department of Surgery and
4 Department of Laboratory Medicine, Shinshu University, 3–1–1 Asahi, Matsumoto 390–8621, Japan
Helicobacter pylori (Hp) is thought to be a stomach carcinogen from epidemiological findings. To determine the effects of infection with the bacteria on experimental carcinogenesis, a study of the glandular stomach of Mongolian gerbils (MGs) was performed. Male MGs were treated with N-methyl-N'-nitro-N-nitrosoguanidine followed by inoculation with Hp or infected with Hp followed by N-methyl-N'-nitro-N-nitrosoguanidine administration. Animals were killed at week 50, and their excised stomachs underwent microbiological and histopathological examinations. In addition, a serological investigation was performed. The incidences of adenocarcinomas were significantly higher in animals treated with 60 or 300 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine for 10 weeks followed by Hp inoculation or Hp followed by 20 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine for 30 weeks than in the respective controls. Moreover, tumour-bearing animals had higher titres of anti-Hp antibodies than tumour-free animals. Of interest was the finding that a dose of 100 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine given to infected gerbils eradicated the Hp in about half the animals, with a concomitant reduction in the promoting effect. No tumours were found in animals infected with Hp without N-methyl-N'-nitro-N-nitrosoguanidine or non-treated gerbils. Hp infection enhances glandular stomach carcinogenesis in MGs treated with N-methyl-N'-nitro-N-nitrosoguanidine. Animals with high titres of anti-Hp antibodies are at greatest risk of developing neoplasms.
Abbreviations: Hp, Helicobacter pylori; MG, Mongolian gerbil; MNU, N-methyl-N-nitrosourea; MNNG, N-methyl-N'-nitro-N-nitrosoguanidine; PBS, phosphate-buffered saline.
5 To whom correspondence should be addressed at: Laboratory of Pathology, Aichi Cancer Center Research Institute, Aichi, JapanEmail: mtatemat{at}aichigw.aichi-cc.pref.aichi.jp
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