The effect of nicotine on DNA repair in adult myocytes.
Recent findings have demonstrated that terminally differentiated adult ventricular myocytes are capable of repairing DNA that has been damaged by exposure to oxygen free radicals. Despite the potential importance of DNA repair in cells that may survive many decades after injury, little is known about the mechanisms or regulation of repair. Since tobacco use has a well-defined role in the epidemiology and pathophysiology of heart disease, we tested the effects of nicotine on repair of free radical damaged plasmids by whole-cell protein extracts from adult myocytes. Exposure to a concentration of 25 microM nicotine increased incorporation of (32P)dCTP into damaged plasmids by 16%, and 50 or 100 microM nicotine increased incorporation by 32%. Nicotine did not alter the rate or amount of poly (ADP-ribose) on the major protein acceptor of molecular weight 113-116 kDa. Inhibition of DNA polymerase activity with pyridoxal 5'-phosphate revealed greater plasmid degradation in the presence of nicotine. We conclude that nicotine enhances DNA degradation and the increased repair is a consequence of this greater degradation.
Kozlovskis-Wade
P L
PL
Division of Cardiology, University of Miami School of Medicine, Miami, FL, 33101, USA.
Smets
M J
MJ
Myerburg
R J
RJ
D000818:Animals; D001345:Autoradiography; D002415:Cats; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects*; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects / Q000378:metabolism; D003845:Deoxycytosine Nucleotides / Q000378:metabolism / Q000493:pharmacokinetics; D005609:Free Radicals; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D009206:Myocardium / Q000166:cytology*; D009243:NAD / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D009711:Nucleotides / Q000378:metabolism / Q000493:pharmacokinetics; D010761:Phosphorus Radioisotopes; D010957:Plasmids; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000494:pharmacology
D003845:Deoxycytosine Nucleotides; D005609:Free Radicals; D009711:Nucleotides; D010761:Phosphorus Radioisotopes; D009243:NAD; C024107:2'-deoxycytidine 5'-triphosphate; D011732:Pyridoxal Phosphate; D009538:Nicotine; D011065:Poly(ADP-ribose) Polymerases; D004259:DNA-Directed DNA Polymerase