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PubMed1999

Hypochlorite-induced oxidation of proteins in plasma: formation of chloramines and nitrogen-centred radicals and their role in protein fragmentation.

Activated phagocyte cells generate hypochlorite (HOCl) via the release of H2O2 and the enzyme myeloperoxidase. Plasma proteins are major targets for HOCl, although little information is available about the mechanism(s) of oxidation. In this study the reaction of HOCl (at least 50 microM) with diluted fresh human plasma has been shown to generate material that oxidizes 5-thio-2-nitrobenzoic acid; these oxidants are believed to be chloramines formed from the reaction of HOCl with protein amine groups. Chloramines have also been detected with isolated plasma proteins treated with HOCl. In both cases chloramine formation accounts for approx. 20-30% of the added HOCl. These chloramines decompose in a time-dependent manner when incubated at 20 or 37 degrees C but not at 4 degrees C. Ascorbate and urate remove these chloramines in a time- and concentration-dependent manner, with the former being more efficient. The reaction of fresh diluted plasma with HOCl also gives rise to protein-derived nitrogen-centred radicals in a time- and HOCl-concentration-dependent manner; these have been detected by EPR spin trapping. Identical radicals have been detected with isolated HOCl-treated plasma proteins. Radical formation was inhibited by excess methionine, implicating protein-derived chloramines (probably from lysine side chains) as the radical source. Plasma protein fragmentation occurs in a time- and HOCl-concentration-dependent manner, as evidenced by the increased mobility of the EPR spin adducts, the detection of further radical species believed to be intermediates in protein degradation and the loss of the parent protein bands on SDS/PAGE. Fragmentation can be inhibited by methionine and other agents (ascorbate, urate, Trolox C or GSH) capable of removing chloramines and reactive radicals. These results are consistent with protein-derived chloramines, and the radicals derived from them, as contributing agents in HOCl-induced plasma protein oxidation.

Adult↗
PubMed2003

Nasal lavage fluid examination in diagnostics of occupational allergy to chloramine.

OBJECTIVES: Chloramine T is a known sensitising agent in the occupational environment of health care workers. In cases of occupational hazards induced by this agent, a clinical history may be far from conclusive, hence appropriate provocation tests are absolutely essential. The aim of the study was to evaluate the usefulness of the nasal challenge test in diagnostics of respiratory allergy to chloramine T. MATERIALS AND METHODS: A single-blind, placebo-controlled study was conducted in 6 subjects with chloramine T asthma and rhinitis. Two control groups comprised 7 atopic subjects with asthma and rhinitis and 6 healthy persons. All the controls had negative results of skin prick tests with chloramine T and none displayed any respiratory symptoms under exposure to the agent. A "nasal pool" technique was used to evaluate morphological and biochemical parameters (mast cell tryptase, eosinophil cationic protein, permeability index) in nasal washings before and 30 min, 4 h and 24 h after the provocation with chloramine T and placebo. RESULTS: A significant increase was found in the total count and percentage of eosinophils and basophils, albumin, tryptase and eosinophil cationic protein levels in the nasal lavage fluid from patients with chloramine T respiratory allergy when compared to both control groups. Also a dual asthmatic reaction in 4 patients and an isolated late reaction in 2 cases were observed in chloramine-sensitive subjects. CONCLUSIONS: The results indicate the applicability of the "nasal pool" technique as a diagnostic procedure in chloramine T-induced airway allergy.

Adult↗
PubMed1980

Antimicrobial activity of N-chloramine compounds.

Cellular mechanisms of action of two representative N-chloramines were studied. Both compounds, 3-chloro-4,4-dimethyl-2-oxazolidinone (I) and N-chlorosuccinimide (III), inhibited bacterial growth and exerted profound inhibition of bacterial DNA, RNA, and protein synthesis at a concentration of 10(-5) M. Enzymes containing sulfhydryl groups generally were significantly inhibited by these chloramines at 10(-4) M. Dihydrofolate reductase, which contains no sulfhydryl groups, also was inhibited but at much higher chloramine concentrations (10(-2) M); ribonuclease, which also contains no sulfhydryl groups, was unaffected. All of these inhibitory effects of the chloramines could be prevented if sulfhydryl-containing reagents (mercaptoethanol or dithiothreitol) were added before or together with the chloramine. Once inhibition was produced by the chloramine, it was not reversible by later addition of the sulfhydryl reagents. These results suggest that these chloramines act at sulfhydryl sites as well as at other sites in both cells and purified enzymes.

Anti-Bacterial Agents↗
PubMed2001

Oxidation of NADH by chloramines and chloramides and its activation by iodide and by tertiary amines.

Irreversible oxidation of reduced nicotinamide nucleotides by neutrophil-derived halogen oxidants (HOCl, chloramines, HOBr, etc.) is likely to be a highly lethal process, because of the essential role of NAD(P)H in important cell functions such as mitochondrial electron transport, and control of the cellular thiol redox state by NADPH-dependent glutathione reductase. Chloramines (chloramine-T, NH(2)Cl, etc.) and N-chloramides (N-chlorinated cyclopeptides) react with NADH to generate the same products as HOCl, i.e., pyridine chlorohydrins, as judged from characteristic changes in the NADH absorption spectrum. Compared with the fast oxidation of NADH by HOCl, k approximately 3 x 10(5) M(-1) s(-1) at pH 7.2, the oxidation by chloramines is about five orders of magnitude slower; that by chloramides is about four orders of magnitude slower. Apparent rate constants for oxidation of NADH by chloramines increase with increasing proton or buffer concentration, consistent with general acid catalysis, but oxidation by chloramides proceeds with pH-independent kinetics. In presence of iodide the oxidation of NADH by chloramines or chloramides is faster by at least two orders of magnitude; this is due to reaction of iodide with the N-halogen to give HOI/I(2), the most reactive and selective oxidant for NADH among HOX species. Quinuclidine derivatives (QN) like 3-chloroquinuclidine and quinine are capable of catalyzing the irreversible degradation of NADH by HOCl and by chloramines; QN(+)Cl, the chain carrier of the catalytic cycle, is even more reactive toward NADH than HOCl/ClO(-) at physiological pH. Oxidation of NADH by NH(2)Br proceeds by fast, but complex, biphasic kinetics. A compilation of rate constants for interactions of reactive halogen species with various substrates is presented and the concept of selective reactivity of N-halogens is discussed.

Amines↗
PubMed1987

Effects of chloramine-T on charge movement and fraction of open channels in frog nodes of Ranvier.

The effects of chloramine-T, a substance which partially and irreversibly inhibits inactivation of the Na current (Wang 1984), on the on and off charge movement (Qon and Qoff) and on the relative position of the Qon-E and F-E curves were studied on voltage clamped frog nodes of Ranvier. The decrease of Qoff with increasing pulse duration which is seen in normal fibres was much less pronounced in chloramine-T-treated fibres, i.e. chloramine-T inhibited charge immobilization. Also, the decrease of the time constant tau off which normally accompanies the decrease of Qoff was absent in chloramine-T-treated fibres. A correlation (r2 = 0.80) between the relative tau off and the relative Qoff was observed in chloramine-T-treated fibres. The voltage dependence of the on charge movement, Qon-E, was compared with the voltage dependence of the fraction of open channels, F-E. In normal fibres, the F-E curve rose very steeply and crossed the normalized Qon-E curve so that F greater than Qon/Qon max for E greater than -40 mV. After chloramine-T treatment, the F-E curve rose less steeply and remained below the normalized Qon-E curve at all potentials. The effect of halazone was similar to that of chloramine-T but weaker. The observations about the Qon-E and F-E curve are compared with the findings on the squid giant axon.

Action Potentials↗
PubMed1998

Modulation by chloramine-T of 4-aminopyridine-sensitive transient outward current in rabbit atrial cells.

The effects of an oxidizing agent, chloramine-T, on the 4-aminopyridine-sensitive transient outward current (ITO) were investigated in rabbit atrial myocytes by using patch-clamp techniques. Extracellular application of chloramine-T at 20 microM irreversibly slowed the time course of inactivation of the whole-cell ITO, and increased the peak by 19.3% (n = 19) at +40 mV. At 100 microM, chloramine-T decreased the peak by 22.5% (n = 9) of the control, and subsequently induced a glibenclamide-sensitive time-independent outward K+ current. Under superfusion with dithiothreitol (3 mM), chloramine-T (100 microM) produced no change in ITO. The chloramine-T-induced slowing of ITO inactivation was partially reversed by subsequent application of 3 mM dithiothreitol. In single-channel recordings with the cell-attached patch configuration, chloramine-T (20 microM) increased the open probability of the ITO channel from 0.15 to 0.46 at a potential 100 mV positive to the resting potential, and the mean open lifetime from 5.1 ms to 7.0 ms (n = 5). The unitary current amplitude was not affected. As a result, chloramine-T increased the ensemble current in amplitude and slowed its decay. These results indicated that: (1) inactivation of the native A-type channels of rabbit heart is susceptible to oxidation; and (2) oxidation of ITO channels may contribute to the genesis of arrhythmias.

4-Aminopyridine↗
PubMed1993

Assessment of the carcinogenic potential of chlorinated water: experimental studies of chlorine, chloramine, and trihalomethanes.

BACKGROUND: Water chlorination has been one of the major disease prevention treatments of this century. While epidemiologic studies suggest an association between cancer in humans and consumption of chlorination byproducts in drinking water, these studies have not been adequate to draw definite conclusions about the carcinogenic potential of the individual byproducts. PURPOSE: The purpose of this study was to investigate the carcinogenic potential of chlorinated or chloraminated drinking water and of four organic trihalomethane byproducts of chlorination (chloroform, bromodichloromethane, chlorodibromomethane, and bromoform) in rats and mice. METHODS: Bromodichloromethane, chlorodibromomethane, bromoform, chlorine, or chloramine was administered to both sexes of F344/N rats and (C57BL/6 x C3H)F1 mice (hereafter called B6C3F1 mice). Chloroform was given to both sexes of Osborne-Mendel rats and B6C3F1 mice. Chlorine or chloramine was administered daily in the drinking water for 2 years at doses ranging from 0.05 to 0.3 mmol/kg per day. The trihalomethanes were administered by gavage in corn oil at doses ranging from 0.15 to 4.0 mmol/kg per day for 2 years, with the exception of chloroform, which was given for 78 weeks. RESULTS: The trihalomethanes were carcinogenic in the liver, kidney, and/or intestine of rodents. There was equivocal evidence for carcinogenicity in female rats that received chlorinated or chloraminated drinking water; this evidence was based on a marginal increase in the incidence of mononuclear cell leukemia. Rodents were generally exposed to lower doses of chlorine and chloramine than to the trihalomethanes, but the doses in these studies were the maximum that the animals would consume in the drinking water. The highest doses used in the chlorine and chloramine studies were equivalent to a daily gavage dose of bromodichloromethane that induced neoplasms of the large intestine in rats. In contrast to the results with the trihalomethanes, administration of chlorine or chloramine did not cause a clear carcinogenic response in rats or mice after long-term exposure. CONCLUSION: These results suggest that organic byproducts of chlorination are the chemicals of greatest concern in assessment of the carcinogenic potential of chlorinated drinking water.

Animals↗
PubMed1975

Effect of an exposure to chloramine-T on the immunoreactivity of glucagon.

Various preparations of glucagon treated with chloramine-T under different conditions have been studied with respect to their immunoreactivity toward two different glucagon antisera; one specific for pancreatic glucagon and the other capable of reacting with enteroglucagon as well. The glucagon preparations exposed to chloramine-T for different periods reacted almost identically with the nonspecific antibody whether they were used as tracer or standard. On the contrary, treatment with chloramine-T under severe conditions led to reduced immunoreactivity toward the specific antibody. Inclusion of dimethyl sulfoxide (DMSO) in the chloramine-T reaction resulted in preservation of the immunoreactivity of the treated preparations. The cyanogen bromide cleaved-glucagon, (1-26) homoserine lactone, showed little cross-reactivity with the specific antibody whereas it reacted to a similar extent with the nonspecific antibody as natural glucagon did. Amino acid analysis of the hormone exposed to chloramine-T demonstrated that the methionine residue at position 27 in the glucagon molecule had been oxidized to methionine sulfoxide. In addition, tryptophan had also been affected. DMSO protected methionine and tryptophan from the oxidative action of chloramine-T. We postulate from these results that the change in the immunoreactivity toward the specific antibody of glucagon exposed to chloramine-T is mainly due to oxidation of the methionine residue at position 27 in the molecule. The usefulness of DMSO in the iodination process is also discussed.

Animals↗
PubMed2000

Vitamin C protects against and reverses specific hypochlorous acid- and chloramine-dependent modifications of low-density lipoprotein.

Activated phagocytes produce the highly reactive oxidant hypochlorous acid (HOCl) via the myeloperoxidase-catalysed reaction of hydrogen peroxide with chloride ions. HOCl reacts readily with a number of susceptible targets on apolipoprotein B-100 of low-density lipoprotein (LDL), resulting in uncontrolled uptake of HOCl-modified LDL by macrophages. We have investigated the effects of vitamin C (ascorbate), an effective water-soluble antioxidant, on the HOCl- and chloramine-dependent modification of LDL. Co-incubation of vitamin C (25-200 microM) with LDL resulted in concentration-dependent protection against HOCl (25-200 microM)-mediated oxidation of tryptophan and lysine residues, formation of chloramines and increases in the relative electrophoretic mobility of LDL. Vitamin C also partially protected against oxidation of cysteine residues by HOCl, and fully protected against oxidation of these residues by the low-molecular-mass chloramines, N(alpha)-acetyl-lysine chloramine and taurine chloramine, and to a lesser extent monochloramine (each at 25-200 microM). Further, we found that HOCl (25-200 microM)-dependent formation of chloramines on apolipoprotein B-100 was fully reversed by 200 microM vitamin C; however, the loss of lysine residues and increase in relative electrophoretic mobility of LDL were only partially reversed, and the loss of tryptophan and cysteine residues was not reversed. Time-course experiments showed that the reversal by vitamin C of HOCl-dependent modifications became less efficient as the LDL was incubated for up to 4 h at 37 degrees C. These data show that vitamin C not only protects against, but also reverses, specific HOCl- and chloramine-dependent modifications of LDL. As HOCl-mediated LDL modifications have been strongly implicated in the pathogenesis of atherosclerosis, our data indicate that vitamin C could contribute to the anti-atherogenic defence against HOCl.

Ascorbic Acid↗
PubMedDate not supplied

Illness in hemodialysis patients after exposure to chloramine contaminated dialysate.

In September 1987, patients at an outpatient dialysis center were exposed to chloramine contaminated dialysate when the carbon filter in a recently modified water treatment system failed. Forty-one patients required transfusion to treat the resultant hemolytic anemia. Epidemiologic investigation demonstrated that the mortality rate among dialysis center patients increased during the 5 months after chloramine exposure when compared with the 12 months before chloramine exposure, but no deaths could be attributed to the exposure. Chloramine is commonly used as a disinfectant in municipal water supplies, and has previously been reported to cause hemolytic anemia in patients undergoing dialysis. Hemodialysis centers in cities that use chloramine in water supplies must design water treatment systems with adequate means for removing chloramine and must monitor processed water closely to ensure that chloramine contamination does not occur. Dialysis centers that make changes in their water processing systems should evaluate all components of the system before changes are made, and must ensure that after modifications are made, processed water meets the standards set by the Association for Advancement of Medical Instrumentation.

Ambulatory Care Facilities↗
PubMed1988

[Mechanism of the interaction of chloramine with Pseudomonas aeruginosa].

The disinfecting effect of chloramine on P. aeruginosa depends on the concentration of this disinfecting agent, the concentration of P. aeruginosa and the period of exposure, with consideration for the time of attaining equilibrium between the concentration of chloramine and P. aeruginosa, affinity between the disinfectant and bacterial cells, the number of chloramine-binding sites on a bacterial cell, the admixture of organic substances, pH and other environmental characteristics. The interaction of chloramine and P. aeruginosa can be subdivided into two stages: (1) the binding of the disinfectant by bacterial cells and (2) the death of the microbes. The mathematical description of the process of disinfection requires that the main characteristics be expressed in molecular parameters and the time factor be correlated with the terms of attaining the equilibrium for free and bound chloramine. The average number of binding sites for chloramine on a bacterial cell and the affinity constant of chloramine to binding sites have been estimated.

Chloramines↗
PubMed1998

Mass casualties from acute inhalation of chloramine gas.

Mass exposure to chloramine gas has not been reported. We report two groups of 36 patients (72 total) suffering from acute inhalation of chloramine gas. Chloramine gas is produced from mixing common household cleaning agents containing sodium hypochlorite (bleach) and ammonia. The first mass casualty event occurred when 36 male soldiers were exposed during a "cleaning party" in their barracks. Ten days later, 36 female soldiers were exposed in a similar manner and presented to our emergency department. In each event, commonly available cleaning agents--liquid bleach and ammonia--were mixed together, liberating toxic chloramine gas. Nebulized sodium bicarbonate solution has been suggested for treatment of chlorine gas inhalation, but no report of nebulized sodium bicarbonate for treatment of chloramine gas inhalation injury exists. In our series, 22 patients exposed to chloramine gas were treated with a nebulized solution of 3.75% sodium bicarbonate. This treatment made no significant statistical or clinical difference in outcome. We present the largest case series of patients presenting to an emergency department for treatment of acute inhalation of chloramine gas.

Adult↗
PubMed2004

Structure and oxidation capacity of amino acid chloramine derivatives and their effects on platelet aggregation.

Comparison of antiaggregation capacity of N-chloramine acids with different position of the chloramine group in the molecule showed that in the most efficient compounds the distance between the chloramine and carboxyl groups was 3-5 carbon atoms. This feature of antiaggregation activity was not related to the difference in oxidation capacity of N-chloramine acids. It was hypothesized that the revealed structural dependence of antiaggregation activity of N-chloramine acids is determined by the structure of platelet membrane, in particular, the presence of a negatively charged group near the site of interaction between N-chloramine acids and platelet membrane.

Amino Acids↗
PubMed1975

Immunological and biophysical properties of hepatitis B antigen labeled by the chloramine-T and by the lactoperoxidase methods.

Optimal conditions were sought for the radiolabeling of microgram quantities of hepatitis B surface antigen (HBs Ag) employing the chloramine-T or lactoperoxidase iodination procedures. Preparations of HBsAg labeled by these procedures are referred to as chloramine-T preparations and lactoperoxidase preparations, respectively. Labeled HBsAg having specific activities between 10-20 muCi/mug were found to display the greatest degree of sensitivity for unlabeled HBsAg and for anti-HBs using a double-antibody radioimmunoassay (RIA-DA). Increasing the specific activity above this level redulted in a decreased affinity of labeled 1251-HBs Ag for anti-HBs, indicating that soluble antigenic alterations had developed. At equivalent specific activities, chloramine-T preparations competed less effectively for unlabeled HBs Ag than lactoperoxidase preparations, and anti-HBs endpoint titers were slightly reduced, especially among preparations of high specific activity (greater than or equal to 65 muCi/mug). Chloramine-T preparations of HBs Ag (sp. act. 15--30 muCi/mug) showed essentially no antigenic deterioration over a 2-month period at minus 196 degrees C or minus 70 degrees C. Utilization of optimally labeled 1251-HBs Ag has increased the sensitivity of the RIA-DA for unlabeled HBs Ag 30-fold to a level below 1 ng/ml and enhanced antiamine-T method revealed that only the most acidic population was labeled (pH 3.75+/-0.5). In contrast, six antigenic components with distinct pI values ranging from 3.7 to 5.2 were detected by RIA-DA in both unlabeled HBs ag and in the chloramine-T preparation. This indicated that the chloramine-T method did not radically change the relative number or charge of each of the pI populations present in purified preparations of HBs Ag. Analysis of HBs Ag iodinated by the lactoperoxidase procedure revealed the presence of three of four populations of particles with pI values ranging from 3.9 to 4.5, suggesting that this procedure labels HBs Ag more uniformly.

Chloramines↗
PubMed2004

Occurrence and production of chloramines in the chlorination of creatinine in aqueous solution.

Occurrence and production of stable chloramines in the chlorination of creatinine, a constituent of perspiration and urine, in aqueous media were studied. Creatinine (5 x 10(-5)M) was treated with free chlorine in aqueous solutions at molar ratios of 0.5-8 (chlorine/creatinine) at pH 7.0 at room temperature for several days. At lower ratios of chlorine, two stable N-chlorocreatinine derivatives, which were determined as dichloramine fractions by the DPD method, were isolated by HPLC and identified by EI-MS and (1)H-NMR. One was 2-chloroamino-1-methylimidazolin-4-one (creatinine chloramine) and the other was 2-chloroamino-5-hydroxy-1-methylimidazolin-4-one (hydroxycreatinine chloramine). In addition, the formation of methylamine was identified by GC-MS analyses of its imine derivative formed with pentafluorobenzaldehyde. Methylamine forms stable chloramines, which might be determined as mono- and/or di-chloramine fractions together with free chlorine by the DPD method in the reaction mixtures at higher molar ratios of chlorine. In practice, small amounts of methylamine (ca. 19 microg/L) were detected in water samples collected from several swimming pools. Hence, methylamine may be an origin of elusive organic chloramine formed in the chlorination of swimming pools. A probable mechanism of the occurrence and processing of chlorination products of creatinine is suggested.

Benzaldehydes↗
PubMed2001

Kinetics of the reactions of hypochlorous acid and amino acid chloramines with thiols, methionine, and ascorbate.

Thiol oxidation by hypochlorous acid and chloramines is a favorable reaction and may be responsible for alterations in regulatory or signaling pathways in cells exposed to neutrophil oxidants. In order to establish the mechanism for such changes, it is necessary to appreciate whether these oxidants are selective for different thiols as compared with other scavengers. We have measured rate constants for reactions of amino acid chloramines with a range of thiols, methionine, and ascorbate, using a combination of stopped-flow and competitive kinetics. For HOCl, rate constants are too fast to measure directly by our system and values relative to reduced glutathione were determined by competition with methionine. For taurine chloramine, the rate constants for reaction with 5-thio-2-nitrobenzoic acid, GSH, methionine, and ascorbate at pH 7.4 were 970, 115, 39, and 13 M(-1) s(-1), respectively. Values for 10 thiols varied by a factor of 20 and showed an inverse relationship to the pK(a) of the thiol group. Rate constants for chloramines of glycine and N-alpha-acetyl-lysine also showed these relationships. Rates increased with decreasing pH, suggesting a mechanism involving acid catalysis. For hypochlorous acid, rates of reaction with 5-thio-2-nitrobenzoic acid, GSH, cysteine, and most of the other thiols were very similar. Relative reactivities varied by less than 5 and there was no dependence on thiol pK(a). Chloramines have the potential to be selective for different cellular thiols depending on their pK(a). For HOCl to be selective, other factors must be important, or its reactions could be secondary to chloramine formation.

Amino Acids↗
PubMed2005

Kinetic analysis of the role of histidine chloramines in hypochlorous acid mediated protein oxidation.

Hypochlorous acid (HOCl) is a powerful oxidant generated from H(2)O(2) and chloride ions by the heme enzyme myeloperoxidase (MPO) released from activated leukocytes. In addition to its potent antibacterial effects, excessive HOCl production can lead to host tissue damage, with this implicated in human diseases such as atherosclerosis, cystic fibrosis, and arthritis. HOCl reacts rapidly with biological materials, with proteins being major targets. Chlorinated amines (chloramines) formed from Lys and His side chains and alpha-amino groups on proteins are major products of these reactions; these materials are however also oxidants and can undergo further reactions. In this study, the kinetics of reaction of His side-chain chloramines with other protein components have been investigated by UV/visible spectroscopy and stopped flow methods at pH 7.4 and 22 degrees C, using the chloramines of the model compound 4-imidazoleacetic acid and N-alpha-acetyl-histidine. The second-order rate constants decrease in a similar order (Cys > Met > disulfide bonds > Trp approximately alpha-amino > Lys >> Tyr > backbone amides > Arg) to the corresponding reactions of HOCl, but are typically 5-25 times slower. These rate constants are consistent with His side-chain chloramines being important secondary oxidants in HOCl-mediated damage. These studies suggest that formation and subsequent reactions of His side-chain chloramines may be responsible for the targeted secondary modification of selected protein residues by HOCl that has previously been observed experimentally and highlight the importance of chloramine structure on their subsequent reactivity.

Amides↗
PubMed2001

Hypochlorite-induced damage to nucleosides: formation of chloramines and nitrogen-centered radicals.

Stimulated monocytes and neutrophils generate hypochlorite (HOCl) via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl is a key bactericidal agent, but can also damage host tissue. As there is a strong link between chronic inflammation and some cancers, we have investigated HOCl damage to DNA bases. We show that reaction of HOCl with the exocyclic -NH(2) groups of cytidine, adenosine, and guanosine, and the ring NH groups of all bases, yields chloramines (RNHCl/RR'NCl). These are the major initial products. Chloramine decay can be accelerated by UV light and metal ions, and these reactions, together with thermal decomposition, give rise to nucleoside-derived nitrogen-centered radicals. Evidence is presented for the rapid addition of pyrimidine-derived nitrogen-centered radicals to another parent molecule to give dimers. Experiments with nucleoside mixtures show that the propensity for radical formation is cytidine > adenosine = guanosine > uridine = thymidine. These data are inconsistent with the selectivity of HOCl attack and the stability of the resulting chloramines, but can be rationalized if chlorine transfer between bases is rapid and yields the most stable chloramine, with such transfer preceding radical formation. Thus, though thymidine is the major initial site of chloramine formation, rapid chlorine atom transfer generates cytidine and adenosine chloramines. These reactions rationalize the preferential formation of chlorinated cytidine and adenosine in DNA.

Adenosine↗