title: 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.
abstract: 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.
authors.affiliation: Department of Environmental Health, Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Dajun
authors.initials: D
authors.lastname: Tian
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zheng
authors.forename: Songhui
authors.initials: S
authors.lastname: Jiang
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Andersen
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zheng
authors.forename: Gensheng
authors.initials: G
authors.lastname: He
authors.forename: Weidong
authors.initials: W
authors.lastname: Qu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D004781:Environmental Exposure; D005663:Furans / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008387:Marine Toxins; D052998:Microcystins / Q000633:toxicity*; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005663:Furans; D008387:Marine Toxins; D052998:Microcystins; D009153:Mutagens; D017382:Reactive Oxygen Species; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; D008156:Luciferases; C057862:cyanoginosin LR; D005978:Glutathione