RT Journal Article
SR Electronic
T1 Interaction of Anthracyclines with Covalently Closed Circular DNA
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 100
OP 104
VO 17
IS 1
A1 SEYMOUR MONG
A1 VIRGIL H. DUVERNAY
A1 JAMES E. STRONG
A1 STANLEY T. CROOKE
YR 1980
UL http://molpharm.aspetjournals.org/content/17/1/100.abstract
AB The effects of four anthracyclines, adriamycin, carminomycin, aclacinomycin, and marcellomycin, on covalently closed circular PM-2 DNA were studied. At a concentration of 5-10 µM each anthracycline induced conformational changes in PM-2 DNA demonstrated by production of diffuse staining patterns on agarose gels. No significant PM-2 DNA degradation was observed using alkaline sucrose gradient centrifugation, agarose gel electrophoresis analysis nor by a PM-2 DNA fluorescence assay using alkaline denaturation. At higher concentrations (200 µM) and in the presence of reducing agents and high temperature, the anthracyclines were able to degrade PM-2 DNA. Bleomycin A2 was used to test whether the conformational changes induced by anthracyclines were due to random breakage, and Bleomycin A2 was shown to degrade the anthracycline bound PM-2 DNA confirming that the anthracyclines did not degrade PM-2 DNA. Further, these results suggest that anthracyclines bind to PM-2 DNA, and induce significant conformational changes that do not affect Bleomycin A2-induced DNA degradation. ACKNOWLEDGMENTS The authors wish to thank Ms. Julie Durantini for typing this manuscript. We also wish to thank Dr. A. W. Prestayko, Dr. C. H. Huang, and Dr. T. Sawyer for reviewing the manuscript. The support and guidance of Dr. Harris Busch are most appreciated.