Cited by 144Neutrophil, Myeloperoxidase and Oxidative MechanismsRedox biology and oxidative stressWater Treatment and Disinfection

Chlorination of Guanosine and Other Nucleosides by Hypochlorous Acid and Myeloperoxidase of Activated Human Neutrophils

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Masuda, Mitsuharu, Suzuki, Toshinori, Friesen, Marlin D., Ravanat, Jean-Luc, Cadet, Jean, Pignatelli, Brigitte, Nishino, Hoyoku, Ohshima, Hiroshi·2001·Journal of Biological Chemistry

Abstract

Activated human neutrophils secrete myeloperoxidase, which generates HOCl from H2O2 and Cl(-). We have found that various (2'-deoxy)nucleosides react with HOCl to form chlorinated (2'-deoxy)nucleosides, including novel 8-chloro(2'-deoxy)guanosine, 5-chloro(2'-deoxy)cytidine, and 8-chloro(2'-deoxy)adenosine formed in yields of 1.6, 1.6, and 0.2%, respectively, when 0.5 mM nucleoside reacted with 0.5 mM HOCl at pH 7.4. The relative chlorination, oxidation, and nitration activities of HOCl, myeloperoxidase, and activated human neutrophils in the presence and absence of nitrite were studied by analyzing 8-chloro-, 8-oxo-7,8-dihydro-, and 8-nitro-guanosine, respectively, using guanosine as a probe. 8-Chloroguanosine was always more easily formed than 8-oxo-7,8-dihydro- or 8-nitro-guanosine. Using electrospray ionization tandem mass spectrometry, we show that several chlorinated nucleosides including 8-chloro(2'-deoxy)guanosine are formed following exposure of isolated DNA or RNA to HOCl. Micromolar concentrations of tertiary amines such as nicotine and trimethylamine dramatically enhanced chlorination of free (2'-deoxy)nucleosides and nucleosides in RNA by HOCl. As the G-463A polymorphism of the MPO gene, which strongly reduces myeloperoxidase mRNA expression, is associated with a reduced risk of lung cancer, chlorination damage of DNA /RNA and nucleosides by myeloperoxidase and its enhancement by nicotine may be important in the pathophysiology of human diseases associated with tobacco habits.

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Crossref · 10.1074/jbc.m102700200

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Authors
Masuda, M., Suzuki, T., Friesen, M. D., Ravanat, J.-L., Cadet, J., Pignatelli, B., Nishino, H., & Ohshima, H.
Affiliations
  • Kyoto Prefectural University of Medicine (JP)
  • Centre international de recherche sur le cancer (FR)
  • Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
Corresponding author
Ohshima, Hiroshi
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-11
Volume
276
Issue
44
Pages
40486-40496
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2074415956
Cited by
144
References
49
Citations by year
2026: 1 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 9 · 2015: 5 · 2014: 6 · 2013: 6 · 2012: 9
FWCI
3.02
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Water Treatment and Disinfection
Keywords
hypochlorous acid, myeloperoxidase, activated neutrophils, 8-oxo-7,8-dihydroguanosine, tertiary amines, nicotine, trimethylamine, lung cancer risk, tobacco use, oxidative DNA damage
MeSH terms
Animals, Catalysis, Cattle, Chlorine, Guanosine, Humans, Hypochlorous Acid, Methylamines, Peroxidase, Neutrophils, Nucleosides, Neutrophil Activation, Spectrometry, Mass, Electrospray Ionization

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