AI Article Synopsis

  • DNA damage from infections, chronic inflammation, and genotoxic agents is linked to an increased risk of stomach cancer, prompting researchers to explore methods for detecting such damage.
  • The study evaluated a technique to visualize DNA damage responses using γ-H2AX foci in rats treated with various chemical carcinogens and assessed gene expression changes.
  • Findings indicated significant DNA damage, particularly in the pyloric glands after treatment with MNU, with variations in mRNA levels suggesting gland damage and highlighting the potential of γ-H2AX as a biomarker for gastric genotoxicity.

Article Abstract

DNA damage caused by infection and chronic inflammation or exposure to genotoxic agents is considered an important risk factor of gastric carcinogenesis. In this study, we have evaluated a short-term technique to detect DNA damage response to various chemical carcinogens; it involves visualization of Ser 139-phosphorylated histone H2AX (γ-H2AX) foci by immunohistochemistry and expression analysis of other genes by quantitative RT-PCR. Six-week-old male rats were intragastrically administered -methyl--nitrosourea (MNU), 3,2'-dimethyl-4-aminobiphenyl (DMAB), dimethylnitrosamine (DMN), and 1,2- dimethylhydrazine (DMH) for 5 days/week for 4 weeks, using corn oil as a vehicle. Animals were sacrificed at day 28, and their stomachs were excised. γ-H2AX foci formation, indicating DNA double-strand breaks, was observed in the proliferative zone of both fundic and pyloric glands. The number of positive cells per gland was significantly high in pyloric glands in the MNU group and in fundic glands in the MNU and DMAB groups. A significant increase in mRNA level was observed in the DMN group compared with the control, which was in contrast to the decreasing tendency of the mRNA level in the MNU and DMN groups. Apoptotic cells positive for γ-H2AX pan or peripheral nuclear staining were observed on the surface layer of the fundic mucosa in the MNU group. The fundic () mRNA level showed a significant decrease, indicating gland damage. The pyloric mRNA level showed no change. In conclusion, γ-H2AX in combination with other gene expression analyses could be a useful biomarker in a short-term experiment on gastric chemical genotoxicity.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511543PMC
http://dx.doi.org/10.1293/tox.2019-0007DOI Listing

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