Taxol and ionizing radiation: Interaction and mechanisms

Journal Article · Sun May 15 04:00:00 EDT 1994 · International Journal of Radiation Oncology, Biology and Physics; (United States)

DOI:https://doi.org/10.1016/0360-3016(94)90273-9· OSTI ID:7027617

Hei, T K; Geard, C R; Hall, E J ^[1]

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1. Columbia Univ., New York, NY (United States)

Taxol has been shown to be clinically active against several types of human tumors. To assess the potential oncogenic effect of taxol, the in vitro cytotoxic and oncogenic transforming effect of taxol, either alone or in combination with [gamma]-irradiation, were examined. Exponentially growing mouse C3H 10T[sub 1/2] cells were treated with taxol with or without concurrent [gamma]-irradiation. After treatment, cultures were replaced for both clonogenic survival and transformation assays. To determine the effects of taxol on cell cycle kinetics, treated cells were concurrently labelled with bromodeoxyuridine coupled with fluorescein. Accumulated mitotic cells were isolated by the shake-off technique and their plating efficiency and radiosensitivity were determined. Taxol induced a dose dependent toxicity in 10T1/2 cells. In contrast to human tumor cells in culture, the mitotic block induced by a 100 nM dose of taxol in 10T1/2 cells was only partial. While taxol was ineffective in transformant induction, it enhanced the oncogenic transforming potential of [gamma]-rays in a supra-additive manner. The fact that [approximately] 15% of taxol-induced mitotic cells were clonogenically viable and at a cell cycle stage that was most radiosensitive suggests a mechanistic basis for the observed enhancement in transformation incidence by ionizing radiation. Taxol enhances the oncogenicity of radiation by partially blocking the 10T1/2 cells in G[sub 2]/M phases of the cell cycle, phases that are most sensitive to radiation induced oncogenic transformation. 14 refs., 5 figs.

• OSTI ID: 7027617
• Journal Information: International Journal of Radiation Oncology, Biology and Physics; (United States), Journal Name: International Journal of Radiation Oncology, Biology and Physics; (United States) Vol. 29:2; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CELL TRANSFORMATIONS
DRUGS
ELECTROMAGNETIC RADIATION
GAMMA RADIATION
IONIZING RADIATIONS
ONCOGENIC TRANSFORMATIONS
RADIATION EFFECTS
RADIATIONS
SYNERGISM