Different roles of Fpg and Endo III on catechol-induced DNA damage in extended-term cultures of human lymphocytes and L5178Y mouse lymphoma cells.
Catechol is a genotoxic agent assumed to induce DNA damage via the oxidative pathway. Using the comet assay and the repair-specific enzymes formamido pyrimidine glycosylase (Fpg) and endonuclease III (Endo III), we examined the ability of catechol to induce DNA damage in extended-term cultures of human lymphocytes and mouse lymphoma cells. Our results suggest that mouse lymphoma cells are somewhat more sensitive towards catechol-induced DNA damage than the extended-term cultures of human lymphocytes. At high concentrations, the catechol-induced damage seemed to be independent of both Fpg and Endo III, possibly indicating a non-oxidative pathway for the DNA damage (involving, for example, a bulky adduct). The fact that Endo III, but not Fpg, enhanced the DNA damaging effect of catechol, suggests that this metabolite of benzene either mediates oxidation of pyrimidines rather than purines, or that oxidised purines are repaired more efficiently, at least in human lymphocytes. In the latter cells, low concentrations of catechol were found to reduce the DNA migration. Considering the role of Fpg and it's adduct specific detection of 8-oxoguanine, this suggests that a low concentration of catechol has an antioxidative effect reducing the background levels of oxidized purines.
Andersson
Maria A
MA
Department of Pharmaceutical Biosciences, Division of Toxicology, Box 594, BMC, SE-751 24 Uppsala, Sweden.
Hellman
Björn E
BE
D000818:Animals; D002396:Catechols / Q000633:toxicity*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism*; D015247:Deoxyribonuclease HindIII / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008214:Lymphocytes / Q000187:drug effects*; D008223:Lymphoma / Q000473:pathology*; D051379:Mice
D002396:Catechols; D015247:Deoxyribonuclease HindIII; D043382:DNA-Formamidopyrimidine Glycosylase