Comparative studies on repair inhibition by araA, araC and aphidicolin of radiation induced DNA and chromosome damage in rodent cells: comparison with fixation of PLD.
The effect of araA and araC, two specific inhibitors of DNA polymerases alpha and beta, and of aphidicolin, a specific inhibitor of DNA polymerase alpha, on repair of radiation induced damage was studied at the DNA, the chromosome and the cell level in plateau-phase CHO cells. For the experiments at the chromosome level, the premature chromosome condensation technique was used. Repair of total DNA breaks was measured by the unwinding technique and repair of DNA double strand breaks by the neutral filter elution technique. In agreement with the hypothesis that DNA polymerase activity is involved in cellular repair reactions, araA and aphidicolin strongly inhibited repair of radiation induced damage at the DNA and the chromosome level. Also, araC inhibited repair at these endpoints but only to a very limited extent. The relative inhibition of repair by these compounds was similar at the various endpoints studied. At the survival level, araA effectively fixed radiation induced PLD resulting in survival levels corresponding to an exponential survival curve. On the other hand, araC and aphidicolin had only a small effect on cell survival. DNA replication was effectively inhibited by aphidicolin, moderately by araC, and even less by araA. These observations demonstrate that the efficacy of a polymerase inhibitor to inhibit DNA and chromosome repair does not always coincide with its ability to fix radiation induced PLD, or with its ability to inhibit DNA replication. This finding indicates that partly different biochemical pathways may underlie PLD fixation, DNA repair inhibition, and DNA replication inhibition.
Iliakis
G
G
Thomas Jefferson University Hospital, Department of Radiation Oncology and Nuclear Medicine, Philadelphia, PA 19107.
Pantelias
G
G
Okayasu
R
R
Seaner
R
R
D000818:Animals; D016590:Aphidicolin; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002875:Chromosomes / Q000187:drug effects / Q000528:radiation effects*; D006224:Cricetinae; D003561:Cytarabine / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D014740:Vidarabine / Q000494:pharmacology*
D004224:Diterpenes; D003561:Cytarabine; D016590:Aphidicolin; D004247:DNA; D014740:Vidarabine