Doxorubicin inhibits human DNA topoisomerase I
| Autor: | P D Foglesong, C Reckord, S Swink |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Cancer Research
DNA damage Biology Topoisomerase-I Inhibitor Toxicology chemistry.chemical_compound medicine Humans Pharmacology (medical) Doxorubicin Pharmacology Topoisomerase Daunorubicin Molecular biology Kinetics Oncology Biochemistry chemistry DNA Topoisomerases Type I Agarose gel electrophoresis biology.protein DNA supercoil Topoisomerase I Inhibitors Ethidium bromide DNA medicine.drug HeLa Cells |
| Zdroj: | Cancer chemotherapy and pharmacology. 30(2) |
| ISSN: | 0344-5704 |
| Popis: | Purified human DNA topoisomerase I was assayed quantitatively by enzyme titrations with supercoiled pHC624 DNA in the presence of 0-2.0 microM doxorubicin. Supercoiled and relaxed DNAs were resolved by agarose gel electrophoresis in the presence of ethidium bromide, and the percentage of conversion of supercoiled DNA to relaxed DNA was quantified by scanning microdensitometry. The inhibition of DNA topoisomerase I activity was measured at varying concentrations of doxorubicin. Doxorubicin inhibited enzyme activity at an IC50 value (the concentration required to inhibit 50% of the total activity) of 0.8 microM. Similar inhibition was observed for daunomycin, a structurally related anthracycline antitumor drug. These results indicate that anthracyclines inhibit human DNA topoisomerase I activity at concentrations that cause DNA damage and cytotoxicity in vivo. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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