Changes in radiation survival curve parameters in human tumor and rodent cells exposed to Paclitaxel (TAXOL) (Taxol[reg sign])

Journal Article · Wed Jun 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)90456-1· OSTI ID:6809688

Liebmann, J; Cook, J A; Fisher, J; Teague, D; Mitchell, J B ^[1]

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1. National Cancer Institute, Bethesda, MD (United States)

Late G[sub 2] and M are the most radiosensitive phases of the cell cycle. Cells exposed to paclitaxel develop a cell cycle arrest in G[sub 2]/M. These studies were performed to assess the in vitro radiosensitization properties of paclitaxel in human tumor and rodent cell lines. The effect of paclitaxel on the radiation sensitivity of human breast (MCF-7), lung (A549), ovary (OVG-1) adenocarcinoma and Chinese hamster lung fibroblast V79 cells was determined with clonogenic assays. DNA flow cytometry studies were performed to define the cell cycle characteristics of the cells during irradiation. Survival curve parameters for all cell lines were determined with the use of a computer program which represents cell survival after radiation by a linear-quadratic model. All cell lines developed a G[sub 2]/M block after exposure to paclitaxel for 24 h. However, the degree of radiosensitization produced by paclitaxel varied among the cell lines. The maximal sensitizer enhancement ratio (SER) of paclitaxel was 1.8 in MCF-7 cells, 1.6 in OVG-1 cells, and 1.7 in V79 cells. However, no concentration of paclitaxel was able to enhance the radiation sensitivity of A549 cells. Paclitaxel increased the linear ([alpha]) component of the radiation survival curves in all cell lines. The quadratic ([beta]) component was unaffected by paclitaxel in the rodent cells. High concentrations of paclitaxel ([ge] 1000 nM) increased [beta] slightly in the human cell lines but there was considerable variation in the effect of paclitaxel on [beta]. The cells which were sensitized to radiation by paclitaxel had a relatively small baseline [alpha] component, while A549 cells had a large [alpha] component. The authors conclude that paclitaxel is a modest radiosensitizer in some, but not all, human tumor cells. Paclitaxel appears to cause radiosensitization mainly by increasing the [alpha] component of radiation survival curves. 16 refs., 3 figs., 2 tabs.

• OSTI ID: 6809688
• 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. 29:3; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

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