Nunn J W, Chipman J K
School of Biochemistry, University of Birmingham, Edgbaston, UK.
Mutat Res. 1994 Dec;341(2):133-40. doi: 10.1016/0165-1218(94)90094-9.
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.
3-氯-4-（二氯甲基）-5-羟基-2（5H）-呋喃酮（MX）在亚细胞毒性剂量（1.0 - 1000微摩尔；暴露60分钟）下可诱导人白细胞DNA链断裂（通过DNA解旋荧光分析测定）。尽管观察到MX使谷胱甘肽水平呈剂量依赖性下降，但这不一定是所观察到的DNA损伤的致病因素，因为当用马来酸二乙酯将细胞内谷胱甘肽耗竭至对照水平的23%时，未观察到链断裂。此外，链断裂似乎不是由细胞内钙升高介导的，因为未观察到MX诱导的钙库释放。然而，链断裂可能依赖于Ca(2+)，正如用喹啉-2剥夺Ca2+后出现抑制所证明的那样。氯化富里酸（> 3微克/毫升）在亚细胞毒性剂量（高达300微克/毫升）下经长时间暴露（60分钟）也会消耗谷胱甘肽并诱导链断裂。然而，未氯化的物质同样能够导致DNA链断裂（不伴有谷胱甘肽消耗）。因此，MX似乎只是能够诱导DNA链断裂的氯化腐殖物质的多种成分之一。
