title: Oxidative stress and DNA damage induced by a drinking-water chlorination disinfection byproduct 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in mice.
abstract: 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a water chlorine disinfection byproduct, can induce DNA damage (e.g., modification of nucleotides and DNA strand breaks) and subsequent DNA repair in vitro. However, the underlying mechanism(s) how DNA damage is induced by MX is unknown. We hypothesized that MX may cause oxidative stress that leads to DNA damage in vivo. In the present study, we exposed groups of mice to MX at concentrations of 0 (solvent control), 11 (low), 33 (medium) and 99 (high) mg/kg b.w. by single intraperitoneal injection. After treating the mice for 3h, we detected cellular levels of malondialdehyde (MDA) and glutathione (GSH) to assess oxidative stress in the target cells. In addition, we also evaluated DNA damage using single cell gel electrophoresis (SCGE or Comet assay). We found that the levels of DNA damage in all cell types were correlated positively with levels of MDA but negatively with levels of GSH (P<0.05 for all). Also, there were negative correlations between levels of MDA and GSH (r=-0.995 for liver cells, -0.916 for kidney cells, -0.975 for intestine cells, respectively; P<0.05 for all but kidney cells). Our findings suggest that MX may induce DNA damage by the mechanism of causing cellular oxidative stress as measured by increased MDA and decreased GSH, at least in mice.
authors.affiliation: Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Zhou
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Zou
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Lu
mesh_terms: D000818:Animals; D020552:Comet Assay; D004249:DNA Damage; D004202:Disinfectants / Q000633:toxicity*; D005663:Furans / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000633:toxicity; D018508:Water Purification
chemical_list: D004202:Disinfectants; D005663:Furans; D009153:Mutagens; D014874:Water Pollutants, Chemical; D008315:Malondialdehyde; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; D005978:Glutathione