Combined exposure to 3-chloro-4-dichloromethyl-5-hydroxy-2(5H)-furanone and microsytin-LR increases genotoxicity in Chinese hamster ovary cells through oxidative stress
Autor: | Melvin E. Andersen, Weiwei Zheng, Songhui Jiang, Gensheng He, Yuxin Zheng, Weidong Qu, Shu Wang, Dajun Tian, Xia Wang |
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Rok vydání: | 2013 |
Předmět: |
Microcystins
CHO Cells medicine.disease_cause Antioxidants Ames test Superoxide dismutase Cricetulus Cricetinae medicine Environmental Chemistry Animals Furans Luciferases chemistry.chemical_classification Reactive oxygen species Micronucleus Tests biology Cell Death Mutagenicity Tests General Chemistry Environmental exposure Environmental Exposure Molecular biology Glutathione Comet assay Oxidative Stress chemistry Micronucleus test biology.protein Marine Toxins Comet Assay Reactive Oxygen Species Genotoxicity Oxidative stress Mutagens |
Zdroj: | Environmental sciencetechnology. 47(3) |
ISSN: | 1520-5851 |
Popis: | The disinfection byproducts 3-chloro-4-dichloromethyl-5-hydroxy-2(5H)-furanone (MX) and microcystins-LR (MC-LR), which are common contaminants in drinking water, often occur together in water sources in areas with high gastrointestinal tract cancer risks. While often studied alone, combination effects of these compounds are unknown. Here, we examine combined genotoxic responses to mixtures of MX and MC-LR using the Ames test, a cytokinesis-block micronuclei assay, and the comet assay with analysis for interactions by fractional analysis. We also evaluated a possible mechanism of genotoxicity by examining effects of the compounds on markers of oxidative stress. MX and MC-LR administrated jointly at noncytotoxic concentrations demonstrated significant interactions in the Ames test, the micronuclei assay, and the comet assay showing responses greater than those expected for additivity. Moreover, coexposure to MX and MC-LR significantly increased luciferase antioxidant response element activity, intracellular superoxide dismutase, catalase, glutathione, and reactive oxygen species production. In comparison with exposure to either compound alone, the mixtures of MX and MC-LR caused a less than additive effect on oxidative stress. Taken together, these results indicate that MC-LR exacerbates MX genotoxicity in low-dose combined exposure. This interaction may be enhanced by oxidative stress in the combined exposures. |
Databáze: | OpenAIRE |
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