THE EFFECT OF NICOTINE ON RNA REPAIR IN ADULT MYOCYTES

Recent findings have demonstrated that terminally differentiated adult ventricular myocytes are capable of repairing DNA that has been damag ed by exposure to oxygen free radicals, Despite the potential importan ce of DNA repair in cells that may survive many decades after injury, little is known about the mechanisms or regulation of repair. Since to bacco use has a well-defined role in the epidemiology and pathophysiol ogy of heart disease, we tested the effects of nicotine on repair of f ree radical damaged plasmids by whole-cell protein extracts from adult myocytes. Exposure to a concentration of 25 mu M nicotine increased i ncorporation of (P-32)dCTP into damaged plasmids by 16%, and 50 or 100 mu M 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 t he presence of nicotine. We conclude that nicotine enhances DNA degrad ation and the increased repair is a consequence of this greater degrad ation. (C) 1998 Academic Press