Nitrotyrosine formation, apoptosis, and oxidative damage: relationships to nitric oxide production in SJL mice bearing the RcsX tumor
- PMID: 9157968
Nitrotyrosine formation, apoptosis, and oxidative damage: relationships to nitric oxide production in SJL mice bearing the RcsX tumor
Abstract
In SJL mice, growth of RcsX lymphoma cells results in activation of macrophages in the spleen and lymph nodes to produce high levels of NO radical (NO.). We used this experimental model system to study the toxicology of NO. in vivo. To characterize spatial relationships between sites of NO. production and tissue damage, immunohistochemical techniques were developed for simultaneous detection of inducible NO. synthase (iNOS), 3-nitrotyrosine, and apoptosis in spleen and lymph nodes of tumor-bearing animals. Elevated expression of iNOS, presumed to reflect increased NO. production, was associated with a significant increase in frequency of apoptotic nuclei. Both apoptotic nuclei and 3-nitrotyrosine staining were found in cells juxtaposed to iNOS-expressing (ie., NO.-producing) macrophages and also within the macrophages themselves. To assess the extent of DNA damage associated with the response, 8-oxoguanine levels were quantified in DNA extracted from spleens of tumor-bearing mice. No increase in levels of this marker of oxidative DNA damage was found in tissues in which apoptosis and 3-nitrotyrosine levels were highly elevated within specific subsets of cells. Collectively, our results indicate that under the pathophysiological conditions existing in the RcsX tumor-bearing SJL mouse, cellular damage caused by NO. and/or other reactive species produced by activated macrophages is highly localized within cells in close proximity to the activated macrophages.
Similar articles
-
Nitrative stress through formation of 8-nitroguanosine: insights into microbial pathogenesis.Nitric Oxide. 2006 Mar;14(2):101-8. doi: 10.1016/j.niox.2005.10.004. Epub 2005 Nov 23. Nitric Oxide. 2006. PMID: 16309933 Review.
-
Colon epithelial cell death in 2,4,6-trinitrobenzenesulfonic acid-induced colitis is associated with increased inducible nitric-oxide synthase expression and peroxynitrite production.J Pharmacol Exp Ther. 2001 Jun;297(3):915-25. J Pharmacol Exp Ther. 2001. PMID: 11356911
-
Nitric oxide production in SJL mice bearing the RcsX lymphoma: a model for in vivo toxicological evaluation of NO.Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11499-503. doi: 10.1073/pnas.93.21.11499. Proc Natl Acad Sci U S A. 1996. PMID: 8876164 Free PMC article.
-
Nitric oxide in the liver: physiopathological roles.Adv Neuroimmunol. 1995;5(4):379-410. doi: 10.1016/0960-5428(95)00024-0. Adv Neuroimmunol. 1995. PMID: 8746512 Review.
-
Nitric oxide production in relation to spontaneous B-cell lymphoma and myositis in SJL mice.Cancer Res. 1995 Oct 1;55(19):4391-7. Cancer Res. 1995. PMID: 7545539
Cited by
-
Interleukin-22 drives nitric oxide-dependent DNA damage and dysplasia in a murine model of colitis-associated cancer.Mucosal Immunol. 2017 Nov;10(6):1504-1517. doi: 10.1038/mi.2017.9. Epub 2017 Feb 15. Mucosal Immunol. 2017. PMID: 28198364 Free PMC article.
-
Doxorubicin inhibits muscle inflammation after eccentric exercise.J Cachexia Sarcopenia Muscle. 2017 Apr;8(2):277-284. doi: 10.1002/jcsm.12148. Epub 2016 Oct 10. J Cachexia Sarcopenia Muscle. 2017. PMID: 27897404 Free PMC article.
-
In Vitro Oxidation of Collagen Promotes the Formation of Advanced Oxidation Protein Products and the Activation of Human Neutrophils.Inflammation. 2016 Apr;39(2):916-27. doi: 10.1007/s10753-016-0325-3. Inflammation. 2016. PMID: 26920846
-
Increased levels of inosine in a mouse model of inflammation.Chem Res Toxicol. 2013 Apr 15;26(4):538-46. doi: 10.1021/tx300473n. Epub 2013 Apr 4. Chem Res Toxicol. 2013. PMID: 23506120 Free PMC article.
-
A filtered database search algorithm for endogenous serum protein carbonyl modifications in a mouse model of inflammation.Mol Cell Proteomics. 2011 Oct;10(10):M111.007658. doi: 10.1074/mcp.M111.007658. Epub 2011 Jul 18. Mol Cell Proteomics. 2011. PMID: 21768395 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Medical
Molecular Biology Databases