Lack of uniformity in the mutational spectra of chlorohydroxyfuranones in <i>Salmonella typhimurium</i> strain TA100

Hyttinen, Juha M. T.; Niittykoski, Minna; Jansson, Kristian

doi:10.1093/mutage/10.4.321

Cited by 22 publications

(9 citation statements)

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“…Its molecular mutational spectrum is completely different from the other CHFs, inducing primarily G:C ? A:T transitions with a 4:1 preference of the second position of the CCC codon [Hyttinen et al, 1995;Knasmüller et al, 1996]. Fekadu et al [1994] demonstrated that MCA is a directacting mutagen because the addition of a metabolic activation system (rat S-9 mix or bovine serum albumin) in DNA repair assays with E. coli resulted in almost a complete loss of its DNA damaging activity.…”

Section: Discussionmentioning

confidence: 99%

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

Liviac

Creus

Marcos

2009

Environ and Mol Mutagen

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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.

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Section: Discussionmentioning

confidence: 99%

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

Liviac

Creus

Marcos

2009

Environ and Mol Mutagen

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“…MX has caused both of these mutation types in DNA of bacterial and/or mammalian cells in vitro [Watanabe-Akanuma and Ohta, 1994;DeMarini et al, 1995;Hyttinen et al, 1995Hyttinen et al, , 1996Knasmüller et al, 1996], but they have been a minor component of the MX-induced mutations. Three of the four observed mutations were G:C 3 A:T transitions and the fourth was an A:T 3 T:A transversion.…”

Section: Discussionmentioning

confidence: 99%

“…MX has readily induced G:C 3 T:A transversions in the lacZ gene of Escherichia coli (uvrA strain ZA2104) [Watanabe-Akanuma and Ohta, 1994], the hisG46 allele of Saccharomyces typhimurium TA100, TA1535, and TA1950 [DeMarini et al, 1995;Hyttinen et al, 1995;Knasmüller et al, 1996], and the hisG428 allele of S. typhimurium TP2428 [Knasmüller et al, 1996]. Other base substitutions induced by MX have mainly been G:C 3 A:T transitions [Watanabe-Akanuma and Ohta, 1994;DeMarini et al, 1995;Hyttinen et al, 1995;Knasmüller et al, 1996]. Other base substitutions induced by MX have mainly been G:C 3 A:T transitions [Watanabe-Akanuma and Ohta, 1994;DeMarini et al, 1995;Hyttinen et al, 1995;Knasmüller et al, 1996].…”

Section: Introductionmentioning

confidence: 99%

No consistent pattern of mutations inp53 andras genes in liver tumors of rat treated with the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX)

Komulainen¹,

Hakulinen²,

Servomaa³

et al. 2000

Environ. Mol. Mutagen.

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“…Synergism was observed in the frameshift strains, but less than a simple additive effect was observed in the base pair substitution strain. In TA100, MX, CMCF, and MCF induce predominantly G:C 3 T:A transversion [DeMarini et al, 1995;Hyttinen et al, 1995;Knasmüller et al, 1996;Shaughnessy et al, 2000], but MCA induces primarily G:C3 A:T transition Knasmüller et al, 1996]. The types of mutations caused by these CHFs in TA97 have not been reported.…”

Section: His Reverse Mutation Assaymentioning

confidence: 97%

Bacterial and mammalian‐cell genotoxicity of mixtures of chlorohydroxyfuranones, by‐products of water chlorination

Mäki‐Paakkanen¹,

Komulainen²,

Krönberg

2004

Environ and Mol Mutagen

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The genotoxic responses of mixtures of four chlorohydroxyfuranones (CHFs), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), 3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA), 3-chloro- 4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF) and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF), were compared with the genotoxicity of the individual compounds. Genotoxicity was evaluated in the Salmonella reversion assay (Ames test), the in vitro Chinese hamster ovary (CHO) cell Hprt mutation assay, and in the CHO chromosome aberration test. When tested individually, the concentrations of the chemicals that were chosen for the mixtures induced no or only a modest increase in the genotoxic effects, and caused little or no cytotoxicity. In the Ames test, the genotoxic responses caused by the mixtures of CHFs did not follow simple additivity. Synergism was observed with strains TA97 and TA98, and antagonism with strain TA100. In the CHO/Hprt mutation assay, the mutagenic response of the mixtures was inconsistent, with near additivity seen with a mixture of CHFs that resulted in 12% cell survival. In contrast, the four CHFs together consistently caused more structural chromosome damage (mainly chromatid-type breaks and exchanges) compared to the sum of net effects of the four CHFs tested alone. Also, a potentiating effect was consistently seen for the cytotoxicity of the CHF mixtures both in the CHO/Hprt mutation assay and the chromosome aberration test. The present results indicate that the genotoxic effects of CHF mixtures can be greater than additive. Such effects may be worth considering in the cancer risk assessment of chlorinated drinking water.

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Lack of uniformity in the mutational spectra of chlorohydroxyfuranones in Salmonella typhimurium strain TA100

Cited by 22 publications

References 0 publications

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

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

No consistent pattern of mutations inp53 andras genes in liver tumors of rat treated with the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX)

Bacterial and mammalian‐cell genotoxicity of mixtures of chlorohydroxyfuranones, by‐products of water chlorination

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