Mutagen X and chlorinated tap water are recombinagenic in yeast.
ABSTRACT This study determines the effects of a water disinfection by-product, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (also known as mutagen X or MX) and chlorinated tap water on genomic instability in the yeast Saccharomyces cerevisiae. Tap water samples collected from Cherepovets (Russia) and Boston (MA, USA), were extracted using XAD absorption and ethyl acetate elution. MX and these water extracts were then tested for their ability to induce intrachromosomal recombination (deletions or DEL events), interchromosomal recombination (ICR) and aneuploidy (ANEU) using the yeast DEL assay. MX strongly induced DEL, ICR and ANEU events with a positive dose response and no threshold. Cherepovets tap water induced DEL and ICR events while evidence of ANEU induction was weak. The DEL induction potencies were stronger at higher concentrations. The estimated contribution of MX to DEL induction varied from over 50% at low concentrations (which is comparable to a typical contribution of MX to Ames mutagenicity of tap water) to between 2 and 10% at highest concentrations. For Boston tap water, there was only weak evidence of DEL induction and no evidence of ICR and ANEU induction. This is consistent with the results of other studies, which reported much higher concentrations of MX and stronger Ames mutagenicity in Cherepovets tap water than in Boston tap water.
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ABSTRACT: The extremely potent Ames mutagen MX [3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone] has been found to account for a substantial part of the mutagenicity of drinking waters. Some compounds showing structural relationship with MX have been identified in drinking waters, but it has not been investigated whether they are commonly occurring. Therefore, the main purpose of this study was to make a comprehensive survey of the occurrence of such compounds in drinking waters and of their importance as mutagenicity contributors. Drinking water was collected from 35 localities in Finland and from St. Petersburg, Russia. The acidified water samples were processed through XAD-8 resin and eluted with ethyl acetate. The mutagenic activity was measured in the extracts using the Ames Salmonella typhimurium strain TA100 without metabolic activation. In addition, the concentrations of a total of 13 compounds were determined in the extracts using GC/MS in the selected ion monitoring mode. The study confirms that MX is the most important Ames mutagen in chlorine-disinfected drinking waters, accounting for up to 67% of the overall mutagenicity. Furthermore, the study shows that compounds with structural similarities to MX are commonly present in drinking waters, but their total contribution to the overall mutagenicity is on average only 4%.Environmental Science & Technology - ENVIRON SCI TECHNOL. 03/1997; 31(4).
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ABSTRACT: Exposures to water disinfection by-products (DBPs) via ingestion of drinking water, and dermal absorption and inhalation during showering/bathing were assessed in the city of Cherepovets, Russia, which uses heavy chlorination to disinfect organic-rich surface water. Concentrations of DBPs (mean +/- standard deviation) in tap water were the following: total trihalomethanes (THMs) 205 +/- 70 micrograms/l, five haloacetic acids (HAAs) 150 +/- 30 micrograms/l, and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (mutagen X or MX) 160 +/- 50 ng/l. Concentrations of THMs and HAAs exceeded the corresponding US standards by a factor of 2.5, while MX concentrations were the highest ever reported. The mutagenic activity of tap water extracts in the Salmonella TA-100 assay was 14,900 net revertants/l. Concentrations of chloroform in breathing zone air in bathrooms during showering were 330 +/- 260 micrograms/m3, shower room air at an industrial plant 2,600 +/- 1,100 micrograms/m3, and bedrooms of local residents 2 +/- 2 micrograms/m3. The mean concentration of chloroform was 3.2 micrograms/m3 in exhaled air samples collected before showering and 110 micrograms/m3 after showering. Data on water ingestion and water use practices in the general population and for pregnant women were collected using questionnaires and diaries. Due to concerns over microbiological safety of water, average daily consumption of non-boiled tap water in pregnant women was only 0.01 l/day, while consumption of boiled tap water was 0.81 l/day. This resulted in low ingestion exposures to volatile THMs. Inhalation and dermal absorption determined total exposures to these compounds. HAAs and MX persist in boiled water and drinks resulting in high ingestion exposures. Several brands of inexpensive home water filters were tested for removal of these compounds. To demonstrate a method of exposure reduction in a sensitive subpopulation, the most efficient filters were given to a group of pregnant women. These women and a control group of pregnant women without filters maintained water ingestion diaries for two weeks. The use of home filters resulted in reduction of exposures to HAAs by a factor of three and a greater reduction in exposures to MX.International Journal of Hygiene and Environmental Health 11/2003; 206(6):539-51. · 3.05 Impact Factor
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ABSTRACT: 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) induced DNA strand-breakage (measured by fluorometric analysis of DNA unwinding) in human white blood cells at sub-cytotoxic doses (1.0-1000 microM; 60 min exposure). Although a dose-dependent decrease in glutathione levels was observed with MX, this is not necessarily the causative factor in the observed DNA damage, since no strand breakage was seen on depletion of cellular glutathione to 23% of control by diethylmaleate. In addition, the strand scission does not appear to be mediated by elevation of intracellular calcium as no MX-induced release of calcium stores was observed. Strand breakage may, however, be Ca(2+)-dependent as evidenced by inhibition following deprivation of Ca2+ by Quin-2. Chlorinated fulvic acids (> 3 micrograms/ml) also depleted glutathione and induced strand breaks at sub-cytotoxic doses (up to 300 micrograms/ml) on prolonged exposure (60 min). The unchlorinated material was, however, equally able to cause DNA strand breakage (without glutathione depletion). MX appears, therefore, to be only one of a number of components of chlorinated humic substances able to induce DNA strand breakage.Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 12/1994; 341(2):133-40. · 3.90 Impact Factor