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

• Published in: Environmental science & technology Vol. 47; no. 3; pp. 1678 - 1687
• Main Authors: Wang, Shu, Tian, Dajun, Zheng, Weiwei, Jiang, Songhui, Wang, Xia, Andersen, Melvin E, Zheng, Yuxin, He, Gensheng, Qu, Weidong
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 05.02.2013
• Subjects: Animals; Antioxidants - metabolism; Biological and medical sciences; Breath tests; Cell Death - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; Chemical contaminants; CHO Cells; Comet Assay; Cricetinae; Cricetulus; Cytokines; Drinking water; Environmental Exposure; Epidemiology. Vaccinations; Food toxicology; Furans - toxicity; Gastric cancer; General aspects; Glutathione - metabolism; Infectious diseases; Luciferases - metabolism; Medical sciences; Microcystins - toxicity; Micronucleus Tests; Mutagenicity Tests; Mutagens - toxicity; Oxidation; Oxidative stress; Oxidative Stress - drug effects; Reactive Oxygen Species - metabolism; Rodents; Toxicity; Toxicology; Various organic compounds; Drinking water treatment; Oxidative stress; Toxicity; Chlorine Organic compounds; DNA; Furan derivatives; Genotoxicity; Disinfection; In vitro; By product; Toxic association
• ISSN: 0013-936X; 1520-5851
• DOI: 10.1021/es304541a

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.