Interactions of Hypochlorous Acid with Pyrimidine Nucleotides, and Secondary Reactions of Chlorinated Pyrimidines with GSH, NADH, and Other Substrates

Prütz, Walter A.

doi:10.1006/abbi.1997.0440

Cited by 118 publications

(111 citation statements)

References 21 publications

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“…First, increasing doses of free chlorine, which increasingly affected virus viability, did not result in increased viral DNA damage as detected by the ability of the genome to be a template for cPCR. A similar extent of irreversible loss of DNA integrity (ϳ50%) was reported previously for hypochlorite treatment of native dsDNA (21), suggesting that free chlorine may have a limited ability to damage DNA. Second, the apparent DNA damage did not continue to decrease with greater chlorine exposure relative to E1A protein levels.…”

Section: Discussionsupporting

confidence: 84%

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Mechanistic Aspects of Adenovirus Serotype 2 Inactivation with Free Chlorine

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Shisler

Mariñas

2010

Appl Environ Microbiol

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Free chlorine is an effective disinfectant for controlling adenoviruses in drinking water, but little is known about the underlying inactivation mechanisms. The objective of this study was to elucidate the molecular components of adenovirus type 2 (Ad2) targeted by free chlorine during the inactivation process. The effects of free chlorine treatment on several Ad2 molecular components and associated life cycle events were compared to its effect on the ability of adenovirus to complete its life cycle, i.e., viability. Free chlorine treatment of Ad2 virions did not impair their ability to interact with monoclonal antibodies specific for hexon and fiber proteins of the Ad2 capsid, as measured by enzyme-linked immunosorbent assays, nor did it impair their interaction with recombinant, purified Coxsackie-adenovirus receptor (CAR) proteins in vitro. Free chlorine-treated Ad2 virions also retained their ability to bind to CAR receptors on A549 cell monolayers, despite being unable to form plaques, suggesting that free chlorine inactivates Ad2 by inhibiting a postbinding event of the Ad2 life cycle. DNA isolated from Ad2 virions that had been inactivated by free chlorine was able to be amplified by PCR, indicating that genome damage was not the cause of inactivation. However, inactivated Ad2 virions were unable to express E1A viral proteins during infection of A549 host cells, as measured by using immunoblotting. Collectively, these results indicate that free chlorine inactivates adenovirus by damaging proteins that govern life cycle processes occurring after host cell attachment, such as endocytosis, endosomal lysis, or nuclear delivery.

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Section: Discussionsupporting

confidence: 84%

“…Free chlorine has been reported to react with the amine functional groups present on nucleotides (20,21). Thus, we assessed whether free chlorine would inactivate Ad2 virions by reacting with the nucleotides comprising its genome.…”

Section: Effect Of Free Chlorine On Car-adenovirus Interactionsmentioning

confidence: 99%

Mechanistic Aspects of Adenovirus Serotype 2 Inactivation with Free Chlorine

Page

Shisler

Mariñas

2010

Appl Environ Microbiol

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“…HOCl Preparation-The concentration of HOCl was determined spectrophotometrically (Beckman DU-7400) from its absorbance at 292 nm (molar absorption coefficient (⑀) ϭ 350 M Ϫ1 cm Ϫ1 ) at pH 12 (33). Stock solutions, prepared fresh every day, were then diluted in oocyte incubation medium (ND96, containing 100 mM NaCl, 2 mM KCl, 1 mM MgCl 2 , 1.8 mM CaCl 2 , and 10 mM HEPES at pH 7.6 (osmolarity, 200 -220 mosmol)) to the desired final concentration just before each experiment.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Lung Fluid Clearance and Epithelial Na+ Channels by Chlorine, Hypochlorous Acid, and Chloramines

Song¹,

Wei²,

Zhou³

et al. 2010

Journal of Biological Chemistry

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We investigated the mechanisms by which chlorine (Cl 2 ) and its reactive byproducts inhibit Na ؉ -dependent alveolar fluid clearance (AFC) in vivo and the activity of amiloridesensitive epithelial Na ؉ channels (ENaC) by measuring AFC in mice exposed to Cl 2 (0 -500 ppm for 30 min) and Na ؉ and amiloride-sensitive currents (I Na and I amil , respectively) across Xenopus oocytes expressing human ␣-, ␤-, and ␥-ENaC incubated with HOCl (1-2000 M). Both Cl 2 and HOCl-derived products decreased AFC in mice and whole cell and single channel I Na in a dose-dependent manner; these effects were counteracted by serine proteases. Mass spectrometry analysis of the oocyte recording medium identified organic chloramines formed by the interaction of HOCl with HEPES (used as an extracellular buffer). In addition, chloramines formed by the interaction of HOCl with taurine or glycine decreased I Na in a similar fashion. Preincubation of oocytes with serine proteases prevented the decrease of I Na by HOCl, whereas perfusion of oocytes with a synthetic 51-mer peptide corresponding to the putative furin and plasmin cleaving segment in the ␥-ENaC subunit restored the ability of HOCl to inhibit I Na . Finally, I Na of oocytes expressing wild type ␣-and ␥-ENaC and a mutant form of ␤ENaC (S520K), known to result in ENaC channels locked in the open position, were not altered by HOCl. We concluded that HOCl and its reactive intermediates (such as organic chloramines) inhibit ENaC by affecting channel gating, which could be relieved by proteases cleavage.The balance of fluid covering the respiratory and alveolar epithelia is determined in part by the ability of these cells to transport sodium (Na ϩ ) and chloride (Cl Ϫ ) ions in a vectorial fashion. Active Na ϩ reabsorption across lung epithelia requires the coordinated entry of Na ϩ ions through cation-and Na ϩ -selective amiloride-sensitive channels (ENaC) 5 located at the apical membranes, their extrusion across the basolateral membranes by the electrogenic Na ϩ -K ϩ -ATPase, and the passive movement of K ϩ ions through basolateral K ϩ channels. The entry of Na ϩ ions through apical pathways is thought to be the rate-limiting step in this process (1-3). To preserve neutrality, Cl Ϫ ions follow Na ϩ ions both through transcellular and paracellular pathways (4, 5). The coordinated movement of Na ϩ and Cl Ϫ ions creates an oncotic gradient favoring the absorption of alveolar fluid.Injury to either apical or basolateral pathways by partially reduced intermediates may lead to impairment of fluid reabsorption, which in turn may result in pulmonary edema, hypoxemia, and eventually death from respiratory failure (6 -9). One such specie is hypochlorous acid (HOCl) 6 , which may be generated either endogenously or exogenously. Millimolar concentrations of HOCl may be generated by activated neutrophils and eosinophils by the catalytic actions of neutrophil-and eosinophil-derived myeloperoxidases on chloride (Cl Ϫ ) and hydrogen peroxide (H 2 O 2 ) in close proximity of the apical and basolatera...

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“…HOCl and -OCl have been reported to react with a wide variety of biological molecules such as proteins (Hawkins andDavies, 1998 and1999;Hazell et al, 1993 and1994), amino acids (Nightingale et al, 2000), peptides (Heinecke et al, 1993), lipids (Spickett et al, 2000), and DNA (Prutz, 1998) at physiological pH conditions. The CI atom in HOCl and -OCl b ehaves as Cl+, a strong electrophile, and combines with a pair of electrons in parts of the substrate that have high electron densities (Wojtowicz, 1979).…”

Section: Oxidizing Reactionmentioning

confidence: 99%

Mechanisms of Actions of Sodium Hypochlorite in Cleaning and Disinfection Processes

2006

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Sodium hypochlorite (NaOCI) is the most widely used disinfectant in the food industry despite the increasing availability of other disinfectants.Sodium hypochlorite fulfills many requirements as the ideal disinfectant and furthermore it has an excellent cleaning action. The effectiveness of sodium hypochlorite in the cleaning and disinfection processes depends on the concentration of available chlorine and the pH of the solution. Hypochlorous acid (HOCI) is a weak acid and dissociates to the hypochlorite ion (-OCI) and proton (H+) depending on the solution pH. It is generally believed that HOCI is the active species in the germicidal action, whereas the concentration of -OCI is a key factor determining the cleaning efficiency. This implies that the optimal pH region of the germicidal activity of sodium hypochlorite differs from that of its cleaning activity. This paper describes the theory and practice of the cleaning and disinfecting operations based on the use of sodium hypochlorite solution.

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Interactions of Hypochlorous Acid with Pyrimidine Nucleotides, and Secondary Reactions of Chlorinated Pyrimidines with GSH, NADH, and Other Substrates

Cited by 118 publications

References 21 publications

Mechanistic Aspects of Adenovirus Serotype 2 Inactivation with Free Chlorine

Mechanistic Aspects of Adenovirus Serotype 2 Inactivation with Free Chlorine

Inhibition of Lung Fluid Clearance and Epithelial Na+ Channels by Chlorine, Hypochlorous Acid, and Chloramines

Mechanisms of Actions of Sodium Hypochlorite in Cleaning and Disinfection Processes

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