Cited by 278Nitric Oxide and Endothelin EffectsInflammatory mediators and NSAID effectsRedox biology and oxidative stress

Nitric oxide in gastrointestinal epithelial cell carcinogenesis: linking inflammation to oncogenesis

Jaiswal, Meeta, LaRusso, Nicholas F., Gores, Gregory J.·2001·American Journal of Physiology-Gastrointestinal and Liver Physiology

Abstract

Chronic inflammation of gastrointestinal tissues is a well-recognized risk factor for the development of epithelial cell-derived malignancies. Although the inflammatory mediators linking chronic inflammation to carcinogenesis are numerous, current information suggests that nitric oxide (NO) contributes to carcinogenesis during chronic inflammation. Inducible nitric oxide synthase (iNOS), expressed by both macrophages and epithelial cells during inflammation, generates the bioreactive molecule NO. In addition to causing DNA lesions, NO can directly interact with proteins by nitrosylation and nitosation reactions. The consequences of protein damage by NO appear to be procarcinogenic. For example, NO inhibits DNA repair enzymes such as human 8-oxodeoxyguanosine DNA glycosylase 1 and blocks apoptosis via nitrosylation of caspases. These cellular events permit DNA damage to accumulate, which is required for the numerous mutations necessary for development of invasive cancer. NO also promotes cancer progression by functioning as an angiogenesis factor. Strategies to inhibit NO generation during chronic inflammation or to scavenge reactive nitrogen species may prove useful in decreasing the risk of cancer development in chronic inflammatory gastrointestinal diseases.

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Crossref · 10.1152/ajpgi.2001.281.3.g626

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  • Chronic inflammation, including inflammatory bowel disease and Helicobacter pylori-induced gastritis, induces iNOS and generates large quantities of NO, forming nitrosating and oxidant species such as N2O3 and peroxynitrite, which might cause mutagenesis through deamination, nitration of DNA, or inhibition of the DNA repair system.

    “However, chronic inflammation, including inflammatory bowel disease and Helicobacter pylori-induced gastritis induce inducible NOS (iNOS) and generate large quantities of NO [22,146,147], forming nitrosating and oxidant species such as N2O3 and peroxynitrite, which might cause mutagenesis through deamination, nitration of DNA, or inhibition of the DNA repair system [148,149].”

    From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [148]

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Authors
Jaiswal, M., LaRusso, N. F., & Gores, G. J.
Affiliations
Mayo Clinic (US)
Venue
American Journal of Physiology-Gastrointestinal and Liver Physiology
Published
2001-09-01
Volume
281
Issue
3
Pages
G626-G634
ISSN
  • 0193-1857 (ISSN-L)
  • 1522-1547
OpenAlex
W1782967980
Cited by
278
References
138
Citations by year
2026: 4 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 9 · 2020: 4 · 2019: 7 · 2018: 10 · 2017: 9 · 2016: 10 · 2015: 10 · 2014: 19 · 2013: 11 · 2012: 14
FWCI
1.54
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (CA 15083, P30CA015083)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 24031, DK 59427)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
nitric oxide, gastrointestinal carcinogenesis, chronic inflammation, inducible nitric oxide synthase, nitrosylation, nitrosation, DNA repair inhibition, apoptosis, DNA damage, angiogenesis, reactive nitrogen species, inflammatory bowel disease, macrophages
MeSH terms
Animals, Cell Transformation, Neoplastic, Chronic Disease, DNA Damage, DNA Repair, Epithelial Cells, Gastrointestinal Neoplasms, Humans, Inflammation, Neovascularization, Pathologic, Nitric Oxide, Proteins, Tumor Suppressor Protein p53, Apoptosis, Nitric Oxide Synthase, Nitric Oxide Synthase Type II

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