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: MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone), a disinfection by-product present in chlorinated drinking water, is one of the most potent mutagens known. Whereas its genotoxic effects are well documented, the mechanism by which MX exerts such an intense biological effect is still unclear. In order to gain further insight into both the general reactivity of hydroxyhalo furanones, and especially as regards their genotoxicity, here we report an in silico study of the aqueous reactivity of MX and two less powerful analogs (MXY, in general): (3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone -CMCF- and 3-chloro-4-(methyl)-5-hydroxy-2(5H)-furanone -MCF-). The following aspects were investigated: (i) the acid dissociation and isomerization equilibria of MXY, i.e. the species distribution among the possible isomers; (ii) the one-electron reduction potential of MXY; (iii) the guanosine and adenosine alkylation mechanism by MXY, which leads to covalent-DNA adducts and (iv) the redox properties of the adducts. No significant differences were observed between MCF, CMCF and MX, with a single exception: the unimolecular carbon-chlorine cleavage of some MX-nucleotide adducts may afford highly oxidative intermediates, which could be able to remove an electron from contiguous nucleotides directly, especially guanosine. This reaction would provide a pathway for the hypothesized ability of some hydroxyhalofuranones to oxidize DNA.Environmental Science & Technology 11/2012; DOI:10.1021/es303105s · 5.48 Impact Factor
Biophysical Journal 02/2011; 100(3). DOI:10.1016/j.bpj.2010.12.1464 · 3.83 Impact Factor
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ABSTRACT: In China, the safety of drinking water becomes a significant issue due to serious aquatic environmental pollution. The genotoxic levels of raw and finished water from seven typical waterworks located in the five basins in China were then evaluated using umu test. Effect of conventional treatment processes (coagulation, filtration and disinfection) on the genotoxicity and the fate of dissolved organic matter (DOM) was discussed. The results showed that most of the selected finished water presented genotoxicity at or lower than 300 mL water sample exposure dose. The genotoxic effects of finished water were significantly higher than those of raw water. It also exhibited that there existed higher correlation between genotoxic effect and Br(-) than the other water quality parameters. The brominated trihalomethanes played a more important role in finished water genotoxicity than brominated haloacetic acids. The treatment processes could increase the genotoxic effects of finished water, especially for the chlorination treatment. The fluorescence spectra and high performance size-exclusion chromatogram analysis of DOM characters indicated that the proportion of low molecular weight acids, nitrogen containing aromatics, proteinaceous and microbially derived organic matters (200-300 Da) increased during purification processes, which indicated probably the release or formation of drinking water genotoxins.Chemosphere 02/2011; 83(1):14-20. DOI:10.1016/j.chemosphere.2011.01.039 · 3.50 Impact Factor