Ability of Hypochlorous Acid and N-Chloramines to Chlorinate DNA and Its Constituents

Abstract

Myeloperoxidase is a heme enzyme released by activated phagocytes that is responsible for the generation of the strong oxidant hypochlorous acid (HOCl). Although HOCl has potent bactericidal properties and plays an important role in the human immune system, this oxidant also causes damage to tissues, particularly under inflammatory conditions. There is a strong link between chronic inflammation and the incidence of many cancers, which may be associated with the ability of HOCl and related oxidants such as N-chloramines to damage DNA. However, in contrast to HOCl, little is known about the reactivity of N-chloramines with DNA and its constituents. In this study, we examine the ability of HOCl and various N-chloramines to form chlorinated base products on nucleosides, nucleotides, DNA, and in cellular systems. Experiments were performed with N-chloramines formed on Nalpha-acetyl-histidine (His-C), Nalpha-acetyl-lysine (Lys-C), glycine (Gly-C), taurine (Tau-C), and ammonia (Mono-C). Treatment of DNA and related materials with HOCl and His-C resulted in the formation of 5-chloro-2'-deoxycytidine (5CldC), 8-chloro-2'-deoxyadenosine (8CldA) and 8-chloro-2'-deoxyguanosine (8CldG). With the nucleosides, 8CldG was the favored product in each case, and HOCl was the most efficient chlorinating agent. 5Cl(d)C was the most abundant product on exposure of the nucleotides and DNA to HOCl and His-C, with only low levels of chlorinated products observed with Lys-C, Gly-C, Tau-C, and Mono-C. 5CldC was also formed on exposure of smooth muscle cells to either HOCl or His-C. Cellular RNA was also a target for HOCl and His-C, with evidence for the formation of 5-chloro-cytidine (5ClC). This study shows that HOCl and the model N-chloramine, His-C, are able to chlorinate cellular genetic material, which may play a role in the development of various inflammatory cancers.

Tissue-specific response of protein oxidation in the grayling (Thymallus thymallus L.) disinfected by chloramine-T

“…In most cases, the metabolic process is accomplished without injury to the liver itself, whereas many xenobiotic compounds are toxic that can cause liver injury [9]. Accumulating evidence has shown that chloramine-T causes oxidative stress by inducing the generation of reactive oxygen species (ROS) [15]. Sakuma et al (2009) found that monochloramine could increase ROS generation in the cytoplasm of rat primary hepatocyte cultures [12].…”

“…· http://ucom.ru/nm · ISSN 2500-2031 · HOCl and the model N-chloramine are able to chlorinate cellular genetic material, which may play a role in the development of various inflammatory cancers [15]. They have examined the ability of various N-chloramines to form chlorinated base products on nucleosides, nucleotides, DNA, and in cellular systems [15].…”

“…They have examined the ability of various N-chloramines to form chlorinated base products on nucleosides, nucleotides, DNA, and in cellular systems [15]. Stanley et al (2010) examined the ability of HOCl and various N-chloramines to form chlorinated base products on nucleosides, nucleotides, DNA, and in cellular systems. Experiments were performed with N-chloramines formed on Nα-acetyl-histidine (His-C), Nα-acetyl-lysine (Lys-C), glycine (Gly-C), taurine (Tau-C), and ammonia (Mono-C).…”

“…Cellular RNA was also a target for HOCl and His-C, with evidence for the formation of 5-chloro-cytidine. HOCl and the model N-chloramine, His-C, are able to chlorinate cellular genetic material, which may play a role in the development of various inflammatory cancers [15].…”

Chemical and cytokine features of innate immunity characterize serum and tissue profiles in inflammatory bowel disease

“…MPO also produces chlorinating species that react with DNA to form chlorinated adducts such as 5-chloro-2′-deoxycytidine (5-Cl-dC) (23), the presence of which was identified in colon tissue of H. hepaticus-infected Rag2 −/− mice (10). This modification of DNA may provide a mechanistic link between neutrophil activity and colitis-associated carcinoma (10,24,25).…”