Molecular Pharmacology, Vol 17, 388-394, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

DNA Damage in Neocarzinostatin-, Macromomycin-, and Bleomycin-Treated SV40 Virions

¹ Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Memorial Institute, 666 Elm Street, Buffalo, New York 14263
² Department of Viral Oncology, Roswell Park Memorial Institute, 666 Elm Street, Buffalo, New York 14263

The DNA strand scission antitumor drugs neocarzinostatin, macromomycin, and bleomycin have been found to introduce single-strand nicks in encapsidated SV40 DNA. The nicking of encapsidated DNA by neocarzinostatin was demonstrated to have occurred within purified SV40 virions rather than as a result of drug-induced leakage of DNA from the virus. The relationship between sulfhydryl agent and reactivity of these drugs with encapsidated SV40 DNA is similar to that reported for naked SV40 DNA. The reactivity of neocarzinostatin at 0.5 µg/ml with naked and encapsidated SV40 form I DNA is quite similar as measured by the conversion of superhelical DNA to the nicked circular duplex form. However, at higher drug levels (1.0-100.0 µg/ml) the encapsidated DNA is less susceptible to further DNA damage.

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ACKNOWLEDGMENTS The authors would like to thank Charlene Van Dusen and Janet Arnone for their excellent technical assistance and Nina Ruth Wright for her aid in editing the manuscript.

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