Genotoxicity analysis of two hydroxyfuranones, byproducts of water disinfection, in human cells treated in vitro

Abstract

In general, water for human consumption is chemically disinfected, usually by adding chlorine. As well as producing safe drinking water however, the chlorine treatment, also results in a number of disinfection byproducts (DBPs). One important class of these DBPs is made up of hydroxyfuranones (HFs). In this article, we report the results of a recent investigation to assess the genotoxicity of two HFs, namely mucobromic acid (MBA) and mucochloric acid (MCA), in cultured human cells. The comet assay is used to measure the induction of primary DNA damage and to determine the DNA repair kinetics and the ability of the tested compounds to cause oxidative damage. In addition, the micronucleus (MN) assay is applied to evaluate chromosome damage. The results of the comet assay reveal that both HFs are clearly genotoxic leading to high levels of DNA breaks, and that MBA is more effective than MCA. According to the comet results, the DNA damage induced by MBA repairs well over time, but not the one induced by MCA. Furthermore, HFs produce high levels of oxidized bases. In contrast, the results from the MN assay, which measures the induction of clastogenic and/or aneugenic effects, are mainly negative for the two HFs tested, although MCA is able to increase significantly the frequency of micronuclei in binucleated TK cells, at the concentration of 10 microM.

Non-enveloped virus reduction with quaternized chitosan nanofibers containing graphene

“…2 The most common disinfection agent is chlorine, which is known to react with natural organic matter (NOM) and create disinfection by-products that are suspected to be carcinogenic. 3,4 Advanced systems of purification include ozone treatment, coagulation, activated carbon filtration, and ultra-and nano-filtration are currently employed in select municipal water systems. 2,5 These methods have many of the same difficulties, including high backpressures of small pore-sized membranes, the ability of small viruses and heavy metals to escape the system, high cost, and the requirement for a large, multistep municipal system.…”

Mutagenic analysis of six disinfection by-products in the Tk gene of mouse lymphoma cells

“…In vitro studies showed that MBA was able to form adducts with adenosine, to induce positive results in the Ames test, and to induce DNA damage in TK6 cells; nevertheless, it was unable to induce significant increases in the frequency of MN, neither in TK6 cells nor in cultured human lymphocytes [33,48,49]. With respect to MCA (the chlorinated hydroxyfuranone), despite its negative results in the MLA, it was reported as a direct-acting mutagen inducing chromosome damage in mammalian cells and plants, showing a high capacity to induce primary DNA damage (comet assay) in mammalian cells [33,[50][51][52].…”

“…With respect to MCA (the chlorinated hydroxyfuranone), despite its negative results in the MLA, it was reported as a direct-acting mutagen inducing chromosome damage in mammalian cells and plants, showing a high capacity to induce primary DNA damage (comet assay) in mammalian cells [33,[50][51][52].…”

“…This unique genotoxic information corresponding to MBA and TBA was previously Table 1 Toxicity and mutagenicity of bromonitromethane (BNM) and trichloronitromethane (TCNM) in mouse lymphoma cells. reported by us [33,34] on TK6 cell cultures, by using the comet assay and the micronucleus test, respectively. We have evaluated three different classes of DBPs and in each class one brominated and one chlorinated compound was included.…”

Genotoxic halofuranones in water: isomerization and acidity of mucohalic acids

“…The considerable contribution of this group of compounds to the observed mutagenicity of chlorinated tap water has received widespread attention 5, 6. Mucochloric acid (MCA, 3,4‐dichloro‐5‐hydroxyfuran‐2(5 H )‐one) and mucobromic acid (MBA, 3,4‐dibromo‐5‐hydroxyfuran‐2(5 H )‐one) are two halohydroxyfuranones that have been shown to be direct genotoxins and potential carcinogens 7–14. DNA adducts of mucohalic acids (MXA) are known, with the isolation of etheno, oxalo etheno, and halopropenal derivatives of guanosine, adenosine, and cytosine 15–22…”