Inhibition of transcription by adriamycin is a consequence of the loss of negative superhelicity in DNA mediated by topoisomerase II.
Adriamycin is commonly used as a chemotherapeutic agent and is known to intercalate into the major groove of DNA and inhibit DNA and RNA synthesis. Results presented in this communication suggest that adriamycin affects topoisomerase cleavage of DNA. The resultant change in negative superhelicity (decrease) is responsible for the decrease in transcription. This process is not dependent on the continued presence of adriamycin. The reaction between topoisomerases, DNA and adriamycin is dose-dependent. The results help to explain the relatively enhanced cytotoxicity of this drug to tumor cells.
Tarr
M
M
Department of Medical Biochemistry, University of Stellenbosch, Tygerberg, South Africa.
van Helden
P D
PD
D000818:Animals; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004278:DNA, Superhelical / Q000187:drug effects* / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics; D066298:In Vitro Techniques; D009690:Nucleic Acid Conformation; D009865:Oocytes / Q000201:enzymology / Q000378:metabolism; D010957:Plasmids; D013698:Templates, Genetic; D014158:Transcription, Genetic / Q000187:drug effects*; D014982:Xenopus laevis
D004278:DNA, Superhelical; D004317:Doxorubicin; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II