Induction of DNA strand breaks by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone and humic substances in relation to glutathione and calcium status in human white blood cells.
3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) induced DNA strand-breakage (measured by fluorometric analysis of DNA unwinding) in human white blood cells at sub-cytotoxic doses (1.0-1000 microM; 60 min exposure). Although a dose-dependent decrease in glutathione levels was observed with MX, this is not necessarily the causative factor in the observed DNA damage, since no strand breakage was seen on depletion of cellular glutathione to 23% of control by diethylmaleate. In addition, the strand scission does not appear to be mediated by elevation of intracellular calcium as no MX-induced release of calcium stores was observed. Strand breakage may, however, be Ca(2+)-dependent as evidenced by inhibition following deprivation of Ca2+ by Quin-2. Chlorinated fulvic acids (> 3 micrograms/ml) also depleted glutathione and induced strand breaks at sub-cytotoxic doses (up to 300 micrograms/ml) on prolonged exposure (60 min). The unchlorinated material was, however, equally able to cause DNA strand breakage (without glutathione depletion). MX appears, therefore, to be only one of a number of components of chlorinated humic substances able to induce DNA strand breakage.
Nunn
J W
JW
School of Biochemistry, University of Birmingham, Edgbaston, UK.
Chipman
J K
JK
D002118:Calcium / Q000378:metabolism*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity; D014881:Water Supply / Q000032:analysis
D005663:Furans; D009153:Mutagens; D014874:Water Pollutants, Chemical; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; D004247:DNA; D005978:Glutathione; D002118:Calcium