Differences in genotoxicity of H(2)O(2) and tetrachlorohydroquinone in human fibroblasts.
During autoxidation of the pentachlorophenol (PCP) metabolite tetrachlorohydroquinone (TCHQ) the semiquinone is formed as well as reactive oxygen species (ROS). It was examined if *OH or the semiquinone are the cause of TCHQ-induced genotoxicity by direct comparison of TCHQ- and H(2)O(2)-induced DNA damage in human cells. All endpoints tested (DNA damage, DNA repair, and mutagenicity) revealed a greater genotoxic potential for TCHQ than for H(2)O(2). In the comet assay, TCHQ induced DNA damage at lower concentrations than H(2)O(2). The damaging rate by TCHQ (tail moment (tm)/concentration) was 10-fold greater than by H(2)O(2). DNA repair was lower for TCHQ than for H(2)O(2) treatment. This was shown by measuring DNA repair in the unscheduled DNA synthesis (UDS) assay and the persistence of the DNA damage in the comet assay. In contrast to H(2)O(2), TCHQ in non-toxic concentrations was mutagenic in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus of V79 cells. Finally, there were also differences observed in cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay) of TCHQ and H(2)O(2). Whereas the TCHQ cytotoxicity was enhanced during a 21h recovery phase, the H(2)O(2) cytotoxicity did not change. The results demonstrated that the pronounced genotoxic properties of TCHQ in human cells were not caused by *OH radicals but more likely by the tetrachlorosemiquinone (TCSQ) radical.
Purschke
Martin
M
Carl von Ossietzky Universität Oldenburg, FB Biologie and ICBM, Postfach 2503, D-26111 Oldenburg, Germany.
Jacobi
Heike
H
Witte
Irene
I
D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D006873:Hydroquinones / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*
D006873:Hydroquinones; D009153:Mutagens; C044578:2,3,5,6-tetrachlorohydroquinone; D004247:DNA; D006861:Hydrogen Peroxide