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Effects of aphidicolin on the repair and fixation of potentially lethal damage sensitive to. beta. -araA

Journal Article · · Int. J. Radiat. Oncol., Biol. Phys.; (United States)
The effects of aphidicolin, a specific inhibitor of DNA polymerase ..cap alpha.., on the repair and fixation of potentially lethal damage (PLD) sensitive to treatment with ..beta..-araA - a drug acting via inhibition of DNA polymerases ..cap alpha.. and ..beta.. - have been studied. Three ..mu..g/ml of aphidicolin given after irradiation did not produce any significant modification in cell survival. More damage was nevertheless fixed by a given concentration of ..beta..-araA in the presence of aphidicolin to a degree that 10 ..mu..M ..beta..-araA given together with 3 ..mu..g/ml aphidicolin produced an effect similar to that of 70 ..mu..M ..beta..-araA given alone. Although aphidicolin significantly enhanced the effectiveness of ..beta..-araA in fixing PLD, it did not significantly increase the sector of lesions affected. Combined treatment with ..beta..-araA and aphidicolin reduced or eliminated the shoulder from the survival curve without affecting the slope, an effect similar to that observed after treatment of cells with ..beta..-araA alone. Based on these results, the necessity of distinction between inhibition of a repair process and fixation of the damage undergoing repair is discussed, as well as the possible involvement of DNA polymerase ..cap alpha.. and ..beta.. in the repair and fixation of the DNA damage that underlies repair of PLD.
Research Organization:
Research Division Cleveland Clinic Foundation, OH
OSTI ID:
5355707
Journal Information:
Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 11:6; ISSN IOBPD
Country of Publication:
United States
Language:
English