The formation of stable organic chloramines during the aqueous chlorination of cytosine and 5-methylcytosine

Gould, Joseph P.; Richards, John T.; Miles, Malcolm G.

doi:10.1016/0043-1354(84)90250-1

Cited by 29 publications

(23 citation statements)

References 5 publications

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“…8-Chlorinated products of 2Ј-deoxyadenosine (28,29) and 2Ј-deoxyguanosine (30) have also been identified in the reaction with HOCl. Alternatively, in contrast to these stable carbon-chlorinated products, the formation of semistable or unstable nitrogen-chlorinated products, chloramines (RNHCl and RRЈNCl), was also observed (31)(32)(33)(34). Unstable nucleoside chloramines, such as thymidine chloramine, are suggested to initiate DNA single and double strand breaks via nitrogencentered radicals and to transfer their chlorine atoms to other nucleosides (35,36).…”

mentioning

confidence: 99%

Endogenous Formation of Novel Halogenated 2′-Deoxycytidine

Kawai

Morinaga

Kondo

et al. 2004

Journal of Biological Chemistry

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A potential role of DNA damage by leukocyte-derived reactive species in carcinogenesis has been suggested. Leukocyte-derived peroxidases, such as myeloperoxidase and eosinophil peroxidase, use hydrogen peroxide and halides (Cl ؊ and Br ؊ ) to generate hypohalous acids (HOCl and HOBr), halogenating intermediates. It has been suggested that these oxidants lead to the formation of halogenated products upon reaction with nucleobases. To verify the consequences of phagocyte-mediated DNA damage at the site of inflammation, we developed a novel monoclonal antibody (mAb2D3) that recognizes the hypohalous acid-modified DNA and found that the antibody most significantly recognized HOCl/HOBr-modified 2-deoxycytidine residues. The immunoreactivity of HOCl-treated oligonucleotide was attenuated by excess methionine, suggesting that chloramine-like species may be the plausible epitopes of the antibody. On the basis of further characterization combined with mass spectrometric analysis, the epitopes of mAb2D3 were determined to be novel N 4 ,5-dihalogenated 2-deoxycytidine residues. The formation of the dihalogenated 2-deoxycytidine in vivo was immunohistochemically demonstrated in the lung and liver nuclei of mice treated with lipopolysaccharides, an experimental inflammatory model. These results strongly suggest that phagocyte-derived oxidants, hypohalous acids, endogenously generate the halogenated DNA bases such as a novel dihalogenated 2-deoxycytidine in vivo. Halogenation (chlorination and/or bromination) of DNA therefore may constitute one mechanism for oxidative DNA damage at the site of inflammation.

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confidence: 99%

Endogenous Formation of Novel Halogenated 2′-Deoxycytidine

Kawai

Morinaga

Kondo

et al. 2004

Journal of Biological Chemistry

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“…These oxidants can chlorinate, oxidize, and nitrate many biological molecules such as proteins and lipids. Recent studies have demonstrated that HOCl reacts with DNA and RNA to form chlorinated bases, including 8-chloroadenine (9, 10) and 5-chlorocytosine (4,11,12). In the presence of nitrite, HOCl, myeloperoxidase, and activated human neutrophils can also nitrate guanosine to form 8-nitroguanosine (8-nitro-Guo) 1 (13).…”

mentioning

confidence: 99%

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

Masuda¹,

Suzuki²,

Friesen³

et al. 2001

Journal of Biological Chemistry

133

119

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Activated human neutrophils secrete myeloperoxidase, which generates HOCl from H 2 O 2 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-nitroguanosine, 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 myeloproxidase 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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“…Patton et al. (49) and Gould et al (50,51) confirmed that cytosine and uracil react with HOCI in aqueous solution to produce the 5-chloro derivatives. 5-Chlorouracil has been shown to be mutagenic.…”

Section: Reactions Of Oxidants/disinfectants With Heterocyclic Compoundsmentioning

confidence: 56%

Occurrence of by-products of strong oxidants reacting with drinking water contaminants--scope of the problem.

Rice¹,

Gomez-Taylor²

1986

Environ Health Perspect

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This paper describes results of a detailed literature review of the organic and inorganic by-products that have been identified as being formed in aqueous solution with four of the strong oxidizing/disinfecting agents commonly employed in drinking water treatment. These agents are: chlorine, chlorine dioxide, chloramine, and ozone. Significant findings include the production of similar nonchlorinated organic oxidation products from chlorine, chlorine dioxide, and ozone. In addition, all three chlorinous oxidants/disinfectants can produce chlorinated by-products under certain conditions. The presence of chloronitrile compounds in drinking waters is indicated to arise from reactions of chlorine or chloramine to amine/amide functions in amino acids or proteinaceous materials, followed by dehydrohalogenation. These nitriles could hydrolyze to produce the corresponding chloroacetic acids. It is concluded that to minimize the presence of oxidation by-products in drinking waters, the concentrations of oxidizable organic/inorganic impurities should be lowered before any oxidizing agent is added.

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The formation of stable organic chloramines during the aqueous chlorination of cytosine and 5-methylcytosine

Cited by 29 publications

References 5 publications

Endogenous Formation of Novel Halogenated 2′-Deoxycytidine

Endogenous Formation of Novel Halogenated 2′-Deoxycytidine

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

Occurrence of by-products of strong oxidants reacting with drinking water contaminants--scope of the problem.

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