Tags

Type your tag names separated by a space and hit enter

Synergistic cell killing by ionizing radiation and topoisomerase I inhibitor topotecan (SK&F 104864).
Cancer Res. 1991 Nov 01; 51(21):5813-6.CR

Abstract

Topotecan (SK&F 104864), a water-soluble analogue of the topoisomerase I inhibitor camptothecin, is currently in Phase II clinical trial for solid tumors. We have characterized topotecan in terms of its effect upon gamma-radiation-induced cell killing. In colony formation experiments, subtoxic concentrations of topotecan (2 microM) potentiated radiation-induced killing of exponentially growing Chinese hamster ovary or P388 murine leukemia cultured cells. Survival curve shoulders were reduced; the slopes of the exponential portions of the curves were decreased to a small extent. D37 and D10 (radiation dose resulting in 37 and 10% survival of colony-forming ability) values were reduced by approximately 60 and 50%, respectively, in the case of Chinese hamster ovary cells. In P388 cells, topotecan reduced D37 by 35 to 40% and D10 by 20 to 25%. Potentiation of radiation-induced cell killing by topotecan was absolutely dependent upon the presence of the topoisomerase I inhibitor during the first few (less than 30) min after irradiation. Association of topoisomerase I with this effect was confirmed in studies of Chinese hamster ovary cells previously made resistant to camptothecin (and cross-resistant to topotecan), resulting in decreased cellular content of topoisomerase I. These cells were found to be 2- to 3-fold hypersensitive to gamma-radiation-induced killing. P388 camptothecin-resistant cells were further sensitized to the lethal effects of ionizing radiation by nontoxic treatment with the topoisomerase II inhibitor novobiocin, consistent with increased dependence of topoisomerase I-deficient cells upon topoisomerase II.

Authors+Show Affiliations

Department of Biomolecular Discovery, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1657371

Citation

Mattern, M R., et al. "Synergistic Cell Killing By Ionizing Radiation and Topoisomerase I Inhibitor Topotecan (SK&F 104864)." Cancer Research, vol. 51, no. 21, 1991, pp. 5813-6.
Mattern MR, Hofmann GA, McCabe FL, et al. Synergistic cell killing by ionizing radiation and topoisomerase I inhibitor topotecan (SK&F 104864). Cancer Res. 1991;51(21):5813-6.
Mattern, M. R., Hofmann, G. A., McCabe, F. L., & Johnson, R. K. (1991). Synergistic cell killing by ionizing radiation and topoisomerase I inhibitor topotecan (SK&F 104864). Cancer Research, 51(21), 5813-6.
Mattern MR, et al. Synergistic Cell Killing By Ionizing Radiation and Topoisomerase I Inhibitor Topotecan (SK&F 104864). Cancer Res. 1991 Nov 1;51(21):5813-6. PubMed PMID: 1657371.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergistic cell killing by ionizing radiation and topoisomerase I inhibitor topotecan (SK&F 104864). AU - Mattern,M R, AU - Hofmann,G A, AU - McCabe,F L, AU - Johnson,R K, PY - 1991/11/1/pubmed PY - 1991/11/1/medline PY - 1991/11/1/entrez SP - 5813 EP - 6 JF - Cancer research JO - Cancer Res VL - 51 IS - 21 N2 - Topotecan (SK&F 104864), a water-soluble analogue of the topoisomerase I inhibitor camptothecin, is currently in Phase II clinical trial for solid tumors. We have characterized topotecan in terms of its effect upon gamma-radiation-induced cell killing. In colony formation experiments, subtoxic concentrations of topotecan (2 microM) potentiated radiation-induced killing of exponentially growing Chinese hamster ovary or P388 murine leukemia cultured cells. Survival curve shoulders were reduced; the slopes of the exponential portions of the curves were decreased to a small extent. D37 and D10 (radiation dose resulting in 37 and 10% survival of colony-forming ability) values were reduced by approximately 60 and 50%, respectively, in the case of Chinese hamster ovary cells. In P388 cells, topotecan reduced D37 by 35 to 40% and D10 by 20 to 25%. Potentiation of radiation-induced cell killing by topotecan was absolutely dependent upon the presence of the topoisomerase I inhibitor during the first few (less than 30) min after irradiation. Association of topoisomerase I with this effect was confirmed in studies of Chinese hamster ovary cells previously made resistant to camptothecin (and cross-resistant to topotecan), resulting in decreased cellular content of topoisomerase I. These cells were found to be 2- to 3-fold hypersensitive to gamma-radiation-induced killing. P388 camptothecin-resistant cells were further sensitized to the lethal effects of ionizing radiation by nontoxic treatment with the topoisomerase II inhibitor novobiocin, consistent with increased dependence of topoisomerase I-deficient cells upon topoisomerase II. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/1657371/Synergistic_cell_killing_by_ionizing_radiation_and_topoisomerase_I_inhibitor_topotecan__SK&F_104864__ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=1657371 DB - PRIME DP - Unbound Medicine ER -