DNA Repair Protein Expression and Oxidative/Nitrosative Stress in Ulcerative Colitis and Sporadic Colorectal Cancer

Anticancer Res. 2021 Jul;41(7):3261-3270. doi: 10.21873/anticanres.15112.

Abstract

Background/aim: Chronic inflammation generates large quantities of reactive oxygen and nitrogen species that damage DNA. DNA repair is important for cellular viability and genome integrity.

Materials and methods: Expression levels of the DNA repair proteins OGG1, XPA, MLH1, PARP1, and XRCC6, which function in base excision repair, nucleotide excision repair, mismatch repair, single-strand break repair and double-strand break repair, respectively, were assessed using immunohistochemistry in ulcerative colitis and sporadic colorectal cancer biopsies. Levels of oxidative/ nitrosative stress biomarkers were also assessed.

Results: Ulcerative colitis and colorectal cancer lesions expressed significantly higher levels of all DNA repair proteins and oxidative/ nitrosative stress biomarkers compared to normal colonic mucosa. Ulcerative colitis had the highest XPA and XRCC6 expression.

Conclusion: Oxidative/nitrosative stress is prevalent in the colon of both diseases. Nucleotide excision repair and non-homologous end-joining double-strand break repair may be compromised in colorectal cancer, but not in ulcerative colitis.

Keywords: 3-nitrotyrosine; 4-hydroxy-2-nonenal; DNA repair proteins; Ulcerative colitis; immunohistochemistry; oxidative/nitrosative stress biomarkers; sporadic colorectal cancer.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Colitis, Ulcerative / genetics*
  • Colitis, Ulcerative / pathology
  • Colon / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA / genetics*
  • DNA Damage / genetics
  • DNA Repair / genetics*
  • DNA-Binding Proteins / genetics*
  • Humans
  • Intestinal Mucosa / pathology
  • Nitrosative Stress / genetics*
  • Oxidation-Reduction
  • Oxidative Stress / genetics*

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • DNA