Mutagen X and chlorinated tap water are recombinagenic in yeast
Departments of Cancer Cell Biology and Environmental Health, Harvard School of Public Health, Boston, MA 02111, USA.Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis (Impact Factor: 3.68). 11/2004; 563(2):159-69. DOI: 10.1016/j.mrgentox.2004.07.005
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: 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, better known by its historical name 'mutagen X' or MX, is a chlorination disinfection byproduct that forms from the reaction of chlorine and humic acids in raw water. MX has been measured in drinking water samples in several countries at levels that ranged from non-detectable to 310 ng/L. Although the concentration of MX in drinking water is typically 100- to 1000-fold lower than other common chlorinated by-products of concern (e.g., trihalomethanes), some have hypothesized that MX might play a role in the increased cancer risks that have been associated with the consumption of chlorinated water. This hypothesis is based on observations that MX, in some test systems, is extremely potent relative to trihalomethanes in inducing DNA damage and altering pathways involved in cell growth, and that in some epidemiological studies increased cancer rates are associated with the bacterial mutagenicity of disinfected water of which MX contributes a significant portion. MX also appears to be more potent than other chlorination by-products in causing cancer in animals. This article reviews the available evidence on the carcinogenicity of MX. MX induced cancer at multiple sites in male and female rats, acted as a tumor initiator and promoter, enhanced tumor yields in genetically modified rodents, induced a myriad of genotoxic effects in numerous in vitro and in vivo test systems, and was a potent inhibitor of gap junction intercellular communication. Although the precise mechanism of MX-induced DNA damage is not known, MX is able to cause DNA damage through an unusual mechanism of ionizing DNA bases due to its extremely high reductive potential. MX may also cause mutations through DNA adduction. This article develops a mean cancer potency estimate for MX of 2.3 (mg/kg-d)(-1) and an upper 95% percentile estimate of 4.5 (mg/kg-d)(-1), and examines the potential health risks posed by this chlorination contaminant in drinking water. A discussion of additional data that would be desirable to better characterize the risks posed by MX and other halogenated hydroxyfuranones follows.
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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.