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 human 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-strand breaks and alkali-labile sites (SSBs). Paracetamol (0.1-1.0 mM) present during post-irradiation incubation approximately doubled the maximum level of UV-induced (1-3 J/m2) SSBs and delayed the completion of repair. Although there were considerable variations between cells prepared from different donors, the level of UV-induced DNA SSBs was always higher with paracetamol. Hydroxyurea (0.3 mM), an inhibitor of ribonucleotide reductase, caused a similar increased accumulation and slow removal of SSBs, whereas cytosine-1-beta-D-arabinofuranoside (Ara C) (10 microM), an inhibitor of DNA polymerases, led to a steady accumulation of DNA SSBs. The increased levels of SSBs caused by paracetamol or hydroxyurea were both completely suppressed by concomitant addition of deoxyribonucleosides; this supports the notion that paracetamol as well as hydroxyurea inhibits ribonucleotide reductase. About the same rates of formation and removal of UV-induced SSBs were observed in T lymphocytes, 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 sensitive to the effect of paracetamol. It is concluded that the inhibition of DNA repair may contribute to the clastogenic effects of paracetamol.
Hongslo
J K
JK
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.
Brunborg
G
G
Steffensen
I L
IL
Holme
J A
JA
D000082:Acetaminophen / Q000633:toxicity*; D016587:Antimutagenic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000187:drug effects* / Q000528:radiation effects*; D003854:Deoxyribonucleotides / Q000494:pharmacology; D006801:Humans; D006918:Hydroxyurea / Q000633:toxicity; D008214:Lymphocytes / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000187:drug effects; D014466:Ultraviolet Rays / Q000009:adverse effects
D016587:Antimutagenic Agents; D004277:DNA, Single-Stranded; D003854:Deoxyribonucleotides; D000082:Acetaminophen; D012264:Ribonucleotide Reductases; D006918:Hydroxyurea