PARACETAMOL INHIBITS UV-INDUCED DNA-REPAIR IN RESTING HUMAN MONONUCLEAR BLOOD-CELLS IN-VITRO

The effects of paracetamol on the repair of DNA damage in resting huma n peripheral mononuclear blood cells (MNC) in vitro were investigated by means of the alkaline elution technique. Low doses of UV light (254 nm, 3 J/m2) caused a transient increase in the amount of DNA single-s trand breaks and alkali-labile sites (SSBs). Paracetamol (0.1-1.0 mM) present during post-irradiation incubation approximately doubled the m aximum level of UV-induced (1-3 J/m2) SSBs and delayed the completion of repair. Although there were considerable variations between cells p repared from different donors, the level of UV-induced DNA SSBs was al ways higher with paracetamol. Hydroxyurea (0.3 mM), an inhibitor of ri bonucleotide reductase, caused a similar increased accumulation and sl ow removal of SSBs, whereas cytosine-1-beta-D-arabinofuranoside (Ara C ) (10 muM), an inhibitor of DNA polymerases, led to a steady accumulat ion of DNA SSBs. The increased levels of SSBs caused by paracetamol or hydroxyurea were both completely suppressed by concomitant addition o f deoxyribonucleosides; this supports the notion that paracetamol as w ell as hydroxyurea inhibits ribonucleotide reductase. About the same r ates of formation and removal of UV-induced SSBs were observed in T ly mphocytes, B lymphocytes and monocytes. In both isolated T lymphocytes and B lymphocytes, paracetamol (0.3 mM) markedly increased the level of DNA SSBs induced by UV, whereas monocytes seemed to be less sensiti ve to the effect of paracetamol. It is concluded that the inhibition o f DNA repair may contribute to the clastogenic effects of paracetamol.