title: Paracetamol increases sensitivity to ultraviolet (UV) irradiation, delays repair of the UNG-gene and recovery of RNA synthesis in HaCaT cells.
abstract: We have studied the effect of low levels of paracetamol (0.3 and 1.0 mM) on gene-specific DNA repair, recovery of total RNA synthesis and cytotoxicity after exposure of human keratinocyte cells (HaCaT) to ultraviolet (UV) irradiation. Repair of cyclobutane pyrimidine dimers (CPDs) was measured in the transcriptionally active uracil-DNA glycosylase (UNG) and c-MYC loci. Repair of both strands in the UNG gene was consistently lower in the presence of paracetamol, but this reduction reached significance only at 8 h after irradiation and no dose-response was observed. For the c-MYC gene, we found no significant effect of paracetamol on the repair of CPDs, possibly because UV-irradiation is known to induce transcription of the c-MYC gene and enhanced transcription coupled repair might counteract a negative effect of paracetamol on global genome repair. A dose-dependent delay in the recovery of total RNA synthesis after UV exposure was observed in the presence of paracetamol, which also caused a 20% increase in UV-induced cytotoxicity after 24 h. Paracetamol had no significant effect on either RNA synthesis or cell survival in the absence of UV after 24 h, but reduced cell survival by approximately 10% (at 0.3 mM) and 50%, (at 1.0 mM) after 96 h exposure. Our results demonstrate that paracetamol may inhibit gene-specific repair of CPDs by affecting global genome repair and that different genes may be differentially affected.
authors.affiliation: UNIGEN Center for Molecular Biology, Norwegian University of Science and Technology, Trondheim.
authors.forename: F
authors.initials: F
authors.lastname: Skorpen
authors.forename: B
authors.initials: B
authors.lastname: Alm
authors.forename: C
authors.initials: C
authors.lastname: Skjelbred
authors.forename: P A
authors.initials: PA
authors.lastname: Aas
authors.forename: H E
authors.initials: HE
authors.lastname: Krokan
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D045647:DNA Glycosylases; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D016259:Genes, myc / Q000187:drug effects / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects*; D009699:N-Glycosyl Hydrolases / Q000235:genetics*; D011740:Pyrimidine Dimers / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D014466:Ultraviolet Rays / Q000009:adverse effects*; D051981:Uracil-DNA Glycosidase
chemical_list: D018712:Analgesics, Non-Narcotic; D011740:Pyrimidine Dimers; D000082:Acetaminophen; D012313:RNA; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase