Induction of mutation in V79 Chinese hamster cells by tetrachlorohydroquinone, a metabolite of pentachlorophenol.
Tetrachlorohydroquinone (TCHQ) and tetrachlorocatechol (TCC), two metabolites of the environmental mutagen and carcinogen pentachlorophenol, were tested without exogenous activation in V79 Chinese hamster cells for the induction of mutation at the hypoxanthine phosphoribosyl transferase (HPRT) locus to 6-thioguanine resistance (TGr) and at the Na/K-ATPase locus to ouabain resistance (OuaR). Treatment was for 24 h at 37 degrees C. TCHQ produced statistically significant increases in the frequency of TGr mutants. The lowest observed effective dose (LOED) was 20 microM, where the relative cloning efficiency was 63%. The relationship between the dose of TCHQ and the frequency of TGr mutants was approximately linear over the range of 0-60 microM with an estimated slope (+/- 95% confidence limits) of 1.1 +/- 0.3 mutants per 10(6) clonable cells per microM. At the highest tested dose of TCHQ, 60 microM, the relative cloning efficiency was reduced to 7%. In contrast to TCHQ, TCC was unable to induce TGr mutants at doses up to 120 microM. The relative cloning efficiency at this dose was 5%. Both TCHQ and TCC were unable to induce OuaR mutants. The results suggest that TCHQ is at least partly responsible for the genotoxic activity of pentachlorophenol. TCHQ can produce reactive oxygen species, which may cause large genetic damage such as deletions, resulting in mutation to TGr but not to OuaR.
Jansson
K
K
Department of Cell Biology, University of Jyväskylä, Finland.
Jansson
V
V
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D004247:DNA / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics; D006873:Hydroquinones / Q000633:toxicity*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000187:drug effects; D066298:In Vitro Techniques; D009152:Mutagenicity Tests; D010042:Ouabain; D013866:Thioguanine
D006873:Hydroquinones; D010042:Ouabain; C044578:2,3,5,6-tetrachlorohydroquinone; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine