Increased levels of 5′,8-Cyclopurine DNA lesions in inflammatory bowel diseases

Annalisa Masi, Paola Fortini, Marios G. Krokidis, Erminia Francesca Romeo, Cinzia Bascietto, Paola De Angelis, Valeria Guglielmi, Chryssostomos Chatgilialoglu

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic inflammation is estimated to be a causative factor in a variety of diseases. Under inflammatory conditions reactive oxygen species (ROS) and nitrogen species (RNS) are released leading to DNA damage accumulation and genomic instability. Purine 5′,8-cyclo-2′-deoxynucleosides (cPu) are oxidative DNA lesions, exclusively derived from the attack of HO radicals, which are known to have cytotoxic and mutagenic properties. Herein, we have analyzed the presence of cPu in genomic DNA isolated from fresh colon and visceral adipose tissue biopsies collected from inflammatory bowel diseases (IBD)-affected patients and severely obese subjects, respectively, versus what observed in the control specimens. In colon biopsies, characterized by a higher gene expression level of inducible nitric oxide synthase (iNOS), a significant increase of 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxo-dA) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) lesions and an accumulation of both diastereomeric cPu have been detected. In contrast, the 8-oxo-dA and 8-oxo-dG levels were extremely lower compared to the colon tissues values and no accumulation of cPu, in the inflamed visceral adipose tissue biopsies isolated from bariatric patients versus the lean counterpart was reported. In addition, in adipose tissue undetectable levels of iNOS have been found. These data suggest a potential involvement of cPu in the colon cancer susceptibility observed in IBD patients.

Original languageEnglish
Article number101562
JournalRedox Biology
Volume34
DOIs
Publication statusPublished - Jul 2020

Keywords

  • Cyclopurines
  • DNA damage
  • Free radicals
  • Inflammatory bowel diseases
  • Obesity
  • Reactive oxygen species

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry

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