The role of hydroxyl radicals in tetrachlorohydroquinone induced DNA strand break formation in PM2 DNA and human fibroblasts.
Tetrachlorohydroquinone (TCHQ), which has previously been identified as a metabolite of pentachlorophenol, induces DNA strand breaks in isolated DNA and in human fibroblasts. Strand break formation in PM2 DNA is prevented by the addition of catalase and the hydroxyl radical scavengers DMSO, ethanol and mannitol, whereas addition of SOD reduced SSB only slightly. Oxygen radicals are formed by the autoxidation of TCHQ to the tetrachlorosemiquinone radical. Desferrioxamine (0.2 mM) completely abolished strand break formation, whereas the metal chelator DETAPAC (1 mM) reduced SSB by only 8.5%. The formation of the semiquinone radical at physiological conditions is shown by ESR spectroscopy. Exposure of human fibroblasts to TCHQ also leads to DNA single strand breaks measured by the alkaline elution assay. These were reduced by addition of 5% DMSO. This indicates that at least part of the strand break formation in human cells is also due to the action of hydroxyl radicals.
Carstens
C P
CP
Fachbereich Biologie, Universität Oldenburg, F.R.G.
Blum
J K
JK
Witte
I
I
D002478:Cells, Cultured; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects*; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006873:Hydroquinones / Q000494:pharmacology*; D006878:Hydroxides / Q000009:adverse effects*; D007700:Kinetics; D009153:Mutagens
D004277:DNA, Single-Stranded; D006873:Hydroquinones; D006878:Hydroxides; D009153:Mutagens; C044578:2,3,5,6-tetrachlorohydroquinone