Assessment of the cytotoxicity and genotoxicity of haloacetic acids using microplate-based cytotoxicity test and CHO/HGPRT gene mutation assay

Zhang, Shaohui; Miao, Dong-Yue; Liu, Ailin; Zhang, Li; Wei, Wei; Xie, Hong; Lu, Wen-Qing

doi:10.1016/j.mrgentox.2010.08.014

Cited by 57 publications

(63 citation statements)

References 39 publications

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“…Some of these products have been shown to be genotoxic in various biological systems [1,6], as well as in humans [7][8][9], while others have been shown to be non-genotoxic carcinogens in animal models [1]. Several epidemiological studies suggest a link between consumption of chlorinated drinking water and reproductive and developmental outcomes, such as increased spontaneous abortions and intrauterine growth retardation [10][11][12][13][14], and bladder and gastrointestinal tract cancers [15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Modulation of cytochrome P450 and induction of DNA damage in Cyprinus carpio exposed in situ to surface water treated with chlorine or alternative disinfectants in different seasons

Canistro

Melega

Ranieri

et al. 2012

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Epidemiological studies have shown an association between consumption of disinfected drinking water and adverse health outcomes. The chemicals used to disinfect water react with occurring organic matter and anthropogenic contaminants in the source water, resulting in the formation of disinfection byproducts (DBPs). The observations that some DBPs are carcinogenic in animal models have raised public concern over the possible adverse health effects for humans. Here, the modulation of liver cytochrome P450-linked monooxygenases (MFO) and the genotoxic effects in erythrocytes of Cyprinus carpio fish exposed in situ to surface drinking water in the presence of disinfectants, such as sodium hypochlorite (NaClO), chlorine dioxide (ClO 2 ) and peracetic acid (PAA), were investigated in winter and summer. A complex induction/suppression pattern of CYP-associated MFOs in winter was observed for all disinfectants. For example, a 3.4-to 15-fold increase was recorded of the CYP2B1/2-linked dealkylation of penthoxyresorufin with NaClO (10 days) and PAA (20 days). In contrast, ClO 2 generated the most notable inactivation, the CYP2E1-supported hydroxylation of p-nitrophenol being decreased up to 71% after 10 days' treatment. In summer, the degree of modulation was modest, with the exception of CYP3A1/2 and CYP1A1 supported MFOs (62% loss after 20 days PAA).The micronucleus (MN) induction in fish circulating erythrocytes was also analysed as an endpoint of genotoxic potential in the same fish population. Significant increases of MN induction were detected at the latest sampling time on fish exposed to surface water treated with chlorinate-disinfectants, both in winter (NaClO) and summer (NaClO and ClO 2 ), while no effect was observed in fish exposed to PAA-treated water.These results show that water disinfection may be responsible for harmful outcomes in terms of MFO perturbation and DNA damage; if extrapolated to humans, they ultimately offer a possible rationale for the increased urinary cancer risk recorded in regular drinking water consumers.

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Section: Introductionmentioning

confidence: 99%

Modulation of cytochrome P450 and induction of DNA damage in Cyprinus carpio exposed in situ to surface water treated with chlorine or alternative disinfectants in different seasons

Canistro

Melega

Ranieri

et al. 2012

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…The comet assay and SOS/umu test are generally used to detect the DNAdamage effects of various compounds and complex water samples [22,25,32]. In previous studies using the comet assay, the extracts of raw water and chlorinated drinking water from Hanjiang River induced the DNA-damage effects [17,28].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous DBPs have been reported to induce the gene-mutation effects in in vitro studies [37][38][39]. In our previous study using the CHO-K1/HGPRT assay, haloacetic acids (HAAs) such as iodoacetic acid (IA), bromoacetic acid (BA), and dibromoacetic acid (DBA) were found to induce strong gene-mutation effects [25].…”

Section: Discussionmentioning

confidence: 99%

“…The cells were grown in Ham's F12 medium containing 10% fetal bovine serum (FBS), 100-U penicillin/mL, and 100-g streptomycin/mL at 37 • C and 5% CO 2 . The HGPRT gene mutation assay without exogenous metabolic activation was performed according to the method as described in our previous study [25]. Briefly, a density of 1 × 10 6 CHO-K1 cells was inoculated in a dish containing Ham's F12 medium (10% FBS).…”

Section: Hgprt Gene Mutant Assaymentioning

confidence: 99%

“…The SOS/umu test is less time-consuming and labor-intensive compared with the comet assay, which has been extensively and effectively used to detect the DNA-damage effects of various genotoxic substances and complex water samples [14,22,23]. The HGPRT gene mutation assay is an excellent microplate-based assay to detect the gene-mutation effects of various compounds including DBPs [24,25]. The micronucleus assay, a multi-end-point assay, detects chromosome breakage, chromosome loss, and chromosome rearrangement, which has been widely to evaluate the chromosome-aberration effects of complex water samples [17,26].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of genotoxic effects caused by extracts of chlorinated drinking water using a combination of three different bioassays

Zeng

Zhang

Liao

et al. 2015

Journal of Hazardous Materials

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Trichloressigsäure und Natriumtrichloracetat [MAK Value Documentation in German language, 2016]

Hartwig

2016

The MAK‐Collection for Occupational Health and Safety

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Trichloroacetic Acid and Sodium Trichloroacetate The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated trichloroacetic acid and sodium trichloroacetate to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available publications are described in detail. After oral application of trichloroacetic acid or the sodium salt, the target organ is the liver with mice being more susceptible than rats. Trichloroacetic acid can be regarded as non‐genotoxic. Trichloroacetic acid is only carcinogenic in the liver of mice, not in other organs or in rats. Humans are much less sensitive to mechanisms regarded to be causative for effects in the liver of male mice. Therefore, trichloroacetic acid and its sodium salt, which acts in vivo like trichloroacetic acid, are not classified as carcinogens or germ cell mutagens. The systemic NOAEL in rats is 32.5 mg/kg bw and day in a 2‐year study, which would correspond to a MAK value of 20 mg/m 3 . However, trichloroacetic acid and sodium trichloroacetate are corrosive to the eye of rabbits. As no inhalation studies are available to judge possible irritating effects on the respiratory tract, phosphorous acid, which is also corrosive to the eye, is used as a read‐across. The irritation strength of the three substances is very similar. Since the MAK value of phosphorous acid is 2 mg/m 3 , and the critical effect of trichloroacetic acid and sodium trichloroacetate is local toxicity, a MAK value of 2 mg/m 3 is also assigned to sodium trichloroacetate. As trichloroacetic acid is a vapour at this concentration range, a corresponding MAK value is set in ml/m 3 . Applying the preferred value approach, a MAK value of 0.2 ml/m 3 corresponding to 1.4 mg/m 3 is derived for trichloroacetic acid, which also takes into account the slightly higher acidity compared to phosphorous acid. As the local effect is critical, both substances are assigned to Peak Limitation Category I with an excursion factor of 1. The NOEL for developmental toxicity in rats is 100 mg sodium trichloroacetate/kg bw and day, corresponding to 100 mg/m 3 . Thus, damage to the embryo or foetus is unlikely when the MAK value is observed and both substances are classified in Pregnancy Risk Group C. For sodium trichloroacetate, but not for trichloroacetic acid, skin contact may contribute significantly to systemic toxicity; sodium trichloroacetate is designated with an “H” notation. Sensitization is not expected from the available data.

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Assessment of the cytotoxicity and genotoxicity of haloacetic acids using microplate-based cytotoxicity test and CHO/HGPRT gene mutation assay

Cited by 57 publications

References 39 publications

Modulation of cytochrome P450 and induction of DNA damage in Cyprinus carpio exposed in situ to surface water treated with chlorine or alternative disinfectants in different seasons

Modulation of cytochrome P450 and induction of DNA damage in Cyprinus carpio exposed in situ to surface water treated with chlorine or alternative disinfectants in different seasons

Evaluation of genotoxic effects caused by extracts of chlorinated drinking water using a combination of three different bioassays

Trichloressigsäure und Natriumtrichloracetat [MAK Value Documentation in German language, 2016]

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