title: Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment.
abstract: OBJECTIVE
  The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation.
  
  
  METHODS
  Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells.
  
  
  RESULTS
  Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect.
  
  
  CONCLUSIONS
  Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.
authors.affiliation: FAP Dental Institute, Tokyo, Japan. fzt02705@nifty.com
authors.forename: Kazue
authors.initials: K
authors.lastname: Yamagishi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Onuma
authors.forename: Yota
authors.initials: Y
authors.lastname: Chiba
authors.forename: Shinya
authors.initials: S
authors.lastname: Yagi
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Aoki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sato
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sugawara
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hosoya
authors.forename: Yasutake
authors.initials: Y
authors.lastname: Saeki
authors.forename: Minoru
authors.initials: M
authors.lastname: Takahashi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Fuji
authors.forename: Takeo
authors.initials: T
authors.lastname: Ohsaka
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Okajima
authors.forename: Kenji
authors.initials: K
authors.lastname: Akita
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Pisol
authors.initials: P
authors.lastname: Senawongse
authors.forename: Akio
authors.initials: A
authors.lastname: Urushiyama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kawai
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shoun
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Ishii
authors.forename: Hiroya
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Madoka
authors.initials: M
authors.lastname: Nakajima
authors.forename: Masaru
authors.initials: M
authors.lastname: Tsuboi
authors.forename: Tateo
authors.initials: T
authors.lastname: Yamanaka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001944:Breath Tests / Q000379:methods; D049109:Cell Proliferation; D002849:Chromatography, Gas; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004058:Diffusion / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D005414:Flatulence / Q000378:metabolism; D005740:Gases / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology / Q000627:therapeutic use; D006862:Hydrogen Sulfide / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism; D015416:Maillard Reaction; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013457:Sulfur Compounds / Q000378:metabolism*; D014183:Transplantation, Heterologous; D056928:X-Ray Absorption Spectroscopy / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D005740:Gases; D013438:Sulfhydryl Compounds; D013457:Sulfur Compounds; C005231:methylmercaptan; D006820:Hyaluronic Acid; D008715:Methionine; D005947:Glucose; D006862:Hydrogen Sulfide