Extensive DNA damage induced by monochloramine in gastric cells

Hidekazu Suzuki, Mikiji Mori, Masayuki Suzuki, Kazushi Sakurai, Soichiro Miura, Hiromasa Ishii

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Abstract

Colonization of Helicobacter pylori (Hp) to gastric mucosa plays an important role for the pathogenesis of gastric mucosal lesions. We previously reported the importance of monochloramine (NH2Cl), which was derived from the interaction between Hp-urease and infiltrated leukocytes, in the course of Hp-associated gastric mucosal injury. While the long-term infection of Hp in the gastric mucosa is known to be one of the virulent factors which closely link to the gastric carcinogenesis, the details of its pathogenetic mechanisms remain speculative. The present study is designed to examine whether a NH2Cl could damage the DNA of gastric cells. Rabbit gastric mucosal cells (RGMC) or KATO III cells were cultured and suspended. Cell suspensions were exposed to HOCl, NH3 or NH2Cl for 15 min to give a final concentration of 0.1 mM. The magnitude of a double strand break of DNA was quantified by measuring the remnant double strand stained by ethidium bromide (EB), and the fluorescence intensity of EB was analyzed by spectrophotometer. Separately, cell nuclei were stained by fluorescent dye (Hoechst No. 33258) in order to evaluate the levels of chromatin condensation evoked by DNA fragmentation. The number of cells with chromatin condensation was counted. During the entire experimental period, more than 85% of cells were persistently viable in all groups. NH2Cl significantly induced the DNA double strand break as well as chromatin condensation in RGMC and KATO III cells (P < 0.05). However, NH3 or HOCl did not induce the DNA double strand break as well as chromatin condensation in both cells. NH2Cl, but not its precursors (NH3 or HOCl), enhanced the levels of DNA injury, suggesting the possible involvement in the carcinogenesis of Hp-associated gastric mucosa.

Original languageEnglish
Pages (from-to)243-248
Number of pages6
JournalCancer Letters
Volume115
Issue number2
DOIs
Publication statusPublished - 1997 May 19

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Keywords

  • Apoptosis
  • Chromatin condensation
  • Helicobacter pylori
  • Leukocyte
  • Urease

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Suzuki, H., Mori, M., Suzuki, M., Sakurai, K., Miura, S., & Ishii, H. (1997). Extensive DNA damage induced by monochloramine in gastric cells. Cancer Letters, 115(2), 243-248. https://doi.org/10.1016/S0304-3835(97)04745-9