Dahlhaus M, Almstadt E, Henschke P, Lüttgert S, Appel K E
Division for Plant Protection Products and Pesticides, Federal Institute for Health Protection of Consumers and Veterinary Medicine, Berlin, Germany.
Mutat Res. 1995 Jun;329(1):29-36. doi: 10.1016/0027-5107(95)00014-a.
The biocide pentachlorophenol (PCP) is in part metabolized, by microsomal enzymes, to tetrachloro-p-hydroquinone (TCHQ), which easily oxidizes to its semiquinone radical. Redox cycling of this compound produces reactive oxygen species (ROS) which ultimately may damage cellular DNA. Here, we report on DNA damage generated by TCHQ in hamster lung fibroblasts (V79 cells) using 8-hydroxy-2-deoxyguanosine (8-OH-dG) as a marker of a major oxidative genetic lesion and measuring the induction of DNA single-strand breaks (DNA SSB) with the aid of the alkaline elution assay. TCHQ was administered to cell cultures in concentrations of 6.25, 12.5, 25, and 50 microM for 1 h. 6.25 and 12.5 microM had no significant effect on both parameters, whereas the higher concentrations resulted in increases of the level of 8-OH-dG (2.3- and 2.0-fold, respectively) and induced DNA SSB. The latter lesion may arise from (i) direct attack of OH., (ii) repair of hydroxylated DNA bases, or (iii) cytotoxic effects. Metabolic transformation of PCP to TCHQ and/or other metabolites with quinoid structures and the subsequent generation of ROS, producing oxidative DNA damage, may play a role in PCP-induced carcinogenicity observed in mice.
杀生物剂五氯苯酚（PCP）部分通过微粒体酶代谢为四氯对苯二酚（TCHQ），TCHQ易氧化为其半醌自由基。该化合物的氧化还原循环产生活性氧（ROS），最终可能损害细胞DNA。在此，我们以8-羟基-2'-脱氧鸟苷（8-OH-dG）作为主要氧化遗传损伤的标志物，并借助碱性洗脱试验测量DNA单链断裂（DNA SSB）的诱导情况，报告了TCHQ在仓鼠肺成纤维细胞（V79细胞）中产生的DNA损伤。将TCHQ以6.25、12.5、25和50微摩尔的浓度施用于细胞培养物1小时。6.25和12.5微摩尔对这两个参数均无显著影响，而较高浓度导致8-OH-dG水平分别增加2.3倍和2.0倍，并诱导产生DNA SSB。后一种损伤可能源于（i）羟基自由基的直接攻击，（ii）羟基化DNA碱基的修复，或（iii）细胞毒性作用。PCP代谢转化为TCHQ和/或其他具有醌结构的代谢物，随后产生活性氧，导致氧化性DNA损伤，这可能在小鼠中观察到的PCP诱导的致癌作用中发挥作用。
