Nitric oxide in gastrointestinal epithelial cell carcinogenesis: linking inflammation to oncogenesis
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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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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NO-Rich Diet for Lifestyle-Related Diseases
Kobayashi, J., Ohtake, K., & Uchida, H. (2015) · Nutrients · doi:10.3390/nu7064911 · Cited by 94 · see citing works
- Authors
- Jaiswal, M., LaRusso, N. F., & Gores, G. J.
- Affiliations
- Mayo Clinic (US)
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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