Glutathione and N-acetylcysteine inactivations of mutagenic 2(5H)-furanones from the chlorination of humics in water

Abstract

The mutagenic 2(5H)-furanones resulting from the chlorination of lignohumic substances in water disinfection and paper pulp bleaching are known to be inactivated by thiols. The objectives of the present study were to characterize the kinetics of an inactivating reaction, isolate and characterize products, and determine their mutagenicity in relation to the starting, mutagenic 2(5H)-furanones. The Salmonella typhimurium (TA100) mutagenicity of mucochloric acid (MCA) had a mean value of 2800 revertants/mumol from four assays and was twice as potent as the C-5 isopropyl ether of MCA (MCA-IPE), whose mutagenicity was determined in the same four assays. A second-order reaction of MCA with GSH at pH 7 was observed. The major product, making up 70% of the total product mixture, was identified as a 1.5:1 mixture of two diastereomers formed by sulfur displacement of the C-4 Cl atom from MCA. The major diastereomer was isolated from the 1.5:1 mixture. Connectivity of GSH to the MCA moiety in the product was established by 2D long-range coupling NMR and fully coupled 13C NMR. On the basis of circular dichroism, the major diastereomer had the S configuration at the hydroxyl-bearing, C-5 ring carbon. MCA-IPE reacted with GSH and N-acetylcysteine (NAC), giving 1:1 mixtures of two diastereomers, again by displacement of the C-4 Cl atom from MCA. A single diastereomer was isolated from the 1:1 MCA-IPE plus NAC reaction. Its structure, determined by X-ray crystallography, had the 5R,8R configuration and was in agreement with the ross structure deduced from the NMR analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

MX, a by‐product of water chlorination, lacks in vivo genotoxicity in gpt delta mice but inhibits gap junctional intercellular communication in rat WB cells

“…Thus, it has been hypothesized that mammalian cells may effectively detoxify chlorohydroxyfuranones, including MX [Daniel et al, 1991;Meier et al, 1996]. In fact, it has been shown that MX is efficiently inactivated by endogenous defensive systems such as those involving glutathione and cysteine [LaLonde and Xie, 1993;Watanabe et al, 1994]. The results of the present study support the conclusion that such defensive systems could be sufficient to detoxify MX ingested in drinking water at concentrations well above environmental levels [Melnick et al, 1997].…”

A toxicological evaluation of a fulvic and humic acids preparation

“…The results of our bacterial reverse mutation test are consistent with those of the majority of previous bacterial reverse mutation experiments on humic test items that had not been subjected to chemical disinfection [ 20 , [23] , [24] , [25] , [26] , [27] , [28] ]; however, Ueno et al explored the effects of ozonation on three different HA samples (one from peat, one from wastewater, and one from soil) in a bacterial reverse mutation test and observed differences in the mutagenic potential of each [ 22 ].…”

“…Indeed, chlorination, under conditions of decreasing pH and adequate HA and chlorine concentrations, of organic non-volatile substances contained in HA and FA is known to result in formation of compounds (such as mucochloric acid and 2,3,3-trichloropropenal) that are mutagenic in bacterial reverse mutation tests. However, in general, these studies have been negative with respect to humic substances that have not undergone disinfection, which were often included as control substances or investigated for other reasons [ 20 , [23] , [24] , [25] , [26] , [27] , [28] ].…”

Spectroscopic studies of D-α-tocopherol concentration-induced transformation in egg phosphatidylcholne vesicles

“…Giant vesicles were used as a model of biomembranes suitable for optical microscopy detection [19] due to their resemblance to cell membranes compared to supported bilayers and monolayers, which are prone to artifacts. Giant liposomes (in the form of unilamellar or multilamellar vesicles) were used as model membrane systems, mainly to study the antioxidant properties of tocopherols and other antioxidants by means of spectroscopic techniques such as fluorescence, confocal microscopy, fluorescence lifetimes, fluorescence energy transfer and NMR [14,[20][21][22][23][24][25]. The investigations were focused on the antioxidation processes as well as on changes in the structural and physicochemical properties of the membrane bilayer.…”