title: Mutagenicity and clastogenicity of extracts of Helicobacter pylori detected by the Ames test and in the micronucleus test using human lymphoblastoid cells.
abstract: Epidemiological studies have demonstrated a close association between infection with Helicobacter pylori (H.pylori) and the development of gastric carcinoma. Chronic H.pylori infection increases the frequency of mutation in gastric epithelial cells. However, the mechanism by which infection of H.pylori leads to mutation in gastric epithelial cells is unclear. We suspected that components in H.pylori may be related to the mutagenic response associated with DNA alkylation, and could be detected with the Ames test using a more sensitive strain for alkylating agents. Our investigation revealed that an extract of H.pylori was mutagenic in the Ames test with Salmonella typhimurium YG7108, which is deficient in the DNA repair of O(6)-methylguanine. The extract of H.pylori may contain methylating or alkylating agents, which might induce O (6)-alkylguanine in DNA. Mutagenicity of the alkylating agents N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine in the Ames test with S.typhimurium TA1535 was enhanced significantly in the presence of the extract of H.pylori. The tested extracts of H.pylori resulted in a significant induction of micronuclei in human-derived lymphoblastoid cells. Heat instability and dialysis resistance of the extracts of H.pylori suggest that the mutagenic component in the extracts of H.pylori is a heat-unstable large molecule or a heat-labile small molecule strongly attached or adsorbed to a large molecule. Proteins in the extracts of H.pylori were subsequently fractionated using ammonium sulphate precipitation. However, all fractions expressed enhancing effects toward MNU mutagenicity. These results suggest the mutagenic component is a small molecule that is absorbed into proteins in the extract of H.pylori, which resist dialysis. Continuous and chronic exposure of gastric epithelial cells to the alkylative mutagenic component from H.pylori chronically infected in the stomach might be a causal factor in the gastric carcinogenesis associated with H.pylori.
authors: Department of Medical Genotoxicology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Department of Genetic Toxicology, Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Kita-ku, Okayama 700-8530, Japan, arimoto@cc.okayama-u.ac.jp.
authors: Sakae
authors: S
authors: Arimoto-Kobayashi
authors: Department of Genetic Toxicology, Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Kita-ku, Okayama 700-8530, Japan.
authors: Kaori
authors: K
authors: Ohta
authors: Department of Medical Genotoxicology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and.
authors: Yuta
authors: Y
authors: Yuhara
authors: Department of Genetic Toxicology, Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Kita-ku, Okayama 700-8530, Japan.
authors: Yuka
authors: Y
authors: Ayabe
authors: Department of Medical Genotoxicology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and.
authors: Tomoe
authors: T
authors: Negishi
authors: Department of Medical Genotoxicology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and.
authors: Keinosuke
authors: K
authors: Okamoto
authors: Department of Medical Technology, Matsushita Memorial Hospital, Moriguchi, Osaka 570-8540, Japan.
authors: Yoshihiro
authors: Y
authors: Nakajima
authors: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kajii-cho Kamigyo-ku, Kyoto 602-8566 Japan.
authors: Takeshi
authors: T
authors: Ishikawa
authors: Department of Medical Genotoxicology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and.
authors: Keiji
authors: K
authors: Oguma
authors: Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University of Science, Ridai-cho Kita-ku, Okayama 700-0005, Japan.
authors: Takanao
authors: T
authors: Otsuka
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000382:microbiology / Q000473:pathology; D002457:Cell Extracts / Q000494:pharmacology*; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D005758:Gastritis, Hypertrophic / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D015162:Micronucleus Tests / Q000379:methods; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013276:Stomach Ulcer / Q000382:microbiology / Q000473:pathology
chemical_list: D002457:Cell Extracts; D009153:Mutagens