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 m M) on gene-specific DNA repair, recovery of total RNA synthesis and cy totoxicity after exposure of human keratinocyte cells (HaCaT) to ultra violet (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 consi stently lower in the presence of paracetamol, but this reduction reach ed significance only at 8 h after irradiation and no dose-response was observed. For the c-MYC gene, we found no significant effect of parac etamol 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 gl obal genome repair. A dose-dependent delay in the recovery of total RN A synthesis after UV exposure was observed in the presence of paraceta mol, which also caused a 20% increase in UV-induced cytotoxicity after 24 h. Paracetamol had no significant effect on either RNA synthesis o r cell survival in the absence of UV after 24 h, but reduced cell surv ival by similar to 10% (at 0.3 mM) and 50% (at 1.0 mM) after 96 h expo sure. Our results demonstrate that paracetamol may inhibit gene-specif ic repair of CPDs by affecting global genome repair and that different genes may be differentially affected. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved.