| 11719101 |
Purschke M, Jacobi H, Witte I: Differences in genotoxicity of H (2) O (2) and tetrachlorohydroquinone in human fibroblasts. Mutat Res. 2002 Jan 15;513(1-2):159-67.
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. |
1(0,0,0,1) |