Paracetamol increases sensitivity to ultraviolet (UV) irradiation, delays repair of the UNG-gene and recovery of RNA synthesis in HaCaT cells

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 cytotoxic after exposure of human keratinocyte cells (HaCaT) to ultra violet (UV) irradiation. Repair of cyclobutane pyrimidine dimers (CPD s) was measured in the transcriptionally active uracil-DNA glycosylas e (UNG) and c-MYC loci. Repair of both strands in the UNG gene was co nsistently lower in the presence of paracetamol, but this reduction r eached significance only at 8 h after irradiation and no dose-respons e was observed. For the c-MYC gene, we found no significant effect of paracetamol on the repair of CPDs, possibly because UV-irradiation i s known to induce transcription of the c-MYC gene and enhanced transc ription coupled repair might counteract a negative effect of paraceta mol on global genome repair. A dose-dependent delay in the recovery o f total RNA synthesis after UV exposure was observed in the presence of paracetamol, which also caused a 20% increase in UV-induced cytoto xicity after 24 h. Paracetamol had no significant effect on either RN A synthesis or cell survival in the absence of UV after 24 h, but red uced 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 repa ir and that different genes may be differentially affected.