Aphidicolin inhibits excision repair of UV-induced pyrimidine photodimers in low serum cultures of mitotic and mitomycin C-induced postmitotic human skin fibroblasts.
The rates of formation and excision of UVC light-induced cyclobutane-type pyrimidine photodimers were determined in cultures of foreskin-derived normal human fibroblasts in mitotic (MF) and mitomycin-C (MMC)-induced postmitotic fibroblasts (PMF). Characteristic morphological changes support the notion that MMC accelerates the differentiation pathway from MF to PMF. In cultures treated with aphidicolin, I am able to show that this inhibitor of alpha and/or delta polymerases significantly inhibits the repair of pyrimidine photodimers in foreskin-derived mitotic and MMC-induced postmitotic fibroblasts in low serum cultures (0.5%) following UVC irradiation. Over the concentration range of 0-2 micrograms/ml of aphidicolin, there is a strong concentration-dependent inhibition of repair in cells treated with 10 J/m2 of UVC and incubated with aphidicolin during the post-incubation time (0-24 h). The results demonstrate that pyrimidine photodimers are repaired in low serum cultures by an alpha- and/or delta-polymerase-dependent pathway. These data also imply that the fibroblast differentiation system is a very useful tool to unravel the complex mechanisms of UV-induced DNA damage and repair.
Niggli
H J
HJ
Cosmital SA, Marly, Switzerland.
D016590:Aphidicolin / Q000494:pharmacology*; D001769:Blood; D002478:Cells, Cultured; D003470:Culture Media; D004260:DNA Repair / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology*; D008938:Mitosis; D011740:Pyrimidine Dimers; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays
D003470:Culture Media; D011740:Pyrimidine Dimers; D016590:Aphidicolin; D016685:Mitomycin