Repair of deoxyribonucleic acid lesions caused by adriamycin and ellipticine.
The intercalating agents adriamycin and ellipticine caused DNA single and double strand breaks and DNA-protein crosslinks in mammalian cells. Ellipticine caused a much higher frequency of each of these lesions than adriamycin, at equitoxic doses. However, adriamycin-induced DNA effects were slowly and incompletely repaired over 24 hr after drug removal while the effects of ellipticine were virtually completely repaired within 30 min. Repair of ellipticine-induced lesions was observed only if cells were diluted ( 100-fold) after drug treatment, suggesting that significant amounts of drug may have been sequestered in the cellular membranes. Cell dilution did not alter the effects of adriamycin. Removal of the DNA lesions was temperature dependent. Finally, the similarity in the rates of repair for DNA single and double strand breaks and DNA-protein crosslinks supports the hypothesis that they are functionally related.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D004611:Ellipticines / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism
D000470:Alkaloids; D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded; D004611:Ellipticines; D009363:Neoplasm Proteins; D004317:Doxorubicin