A comparison of the effects of daunomycin and adriamycin on various DNA polymerases.
The effects of the anthracycline antiboties, daunomycin and adriamycin, on the DNA-directed activities of DNA polymerases from murine sarcoma virus, rat liver (high-molecular-weight species), Escherichia coli, and Micrococcus luteus were determined. Under all conditions tested, these compounds had greater inhibitory effect against the viral polymerase than against cellular polymerase. The inhibition of murine sarcoma virus DNA polymerase by daunomycin was competitive with respect to DNA. For viral DNA polymerase it was concluded that the inhibition was predominatly caused by the interaction of duanomycin with the primer-template DNA. Also, an appreciable reversal of the daunomycin-induced inhibition of this polymerase by an increase in Mg-2+ concentration is consistent with the conclusion derived by competition experiments. In contrast, the inhibition of both rat liver and M. luteus DNA polymerases was essentially noncompetitive with DNA. Also, bacterial enzymes wer e less sensitive to inhibition by these drugs than the virion polymerase. The strong and preferential inhibiton of viral DNA polymerase is discussed in relation to a differential sensitivity of normal as compared to tumor cells observed in some cell lines.
D000818:Animals; D001667:Binding, Competitive; D004247:DNA / Q000378:metabolism; D004254:DNA Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D003630:Daunorubicin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D017988:Gammaretrovirus / Q000201:enzymology; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008274:Magnesium / Q000494:pharmacology; D008837:Micrococcus / Q000201:enzymology; D051381:Rats; D012509:Sarcoma / Q000382:microbiology; D013698:Templates, Genetic
D004317:Doxorubicin; D004247:DNA; D004254:DNA Nucleotidyltransferases; D008274:Magnesium; D003630:Daunorubicin