Subadditive interaction of radiation and Taxol in vitro.
OBJECTIVE
To examine the dependency of Taxol-radiation interactions on the scheduling of the two agents.


METHODS
The human laryngeal squamous cell carcinoma line SCC20 was used for this study. Cells were irradiated as subconfluent cultures using Cs-137 gamma rays at a dose rate of 1.75 Gy/min. Cultures were pretreated with Taxol (7.5 nM for 12 h, S.F. = 0.4) and then irradiated with graded doses followed by either immediate plating or holding for 6 h either in the absence or presence of 7.5 nM Taxol prior to plating for colony-forming ability. Experiments in which cells were irradiated and then exposed to 7.5 nM Taxol for both 12 and 18 h were also performed. Parallel-flow cytometric analyses of cell-cycle distribution of the various treated populations were carried out.


RESULTS
The results indicate that pretreatment with Taxol induced a G2 block which was maintained during 6 h postirradiation holding either in the presence or absence of Taxol. No modification of radiosensitivity in the low-dose region was seen for cells treated with Taxol, irradiated, and plated immediately, with the resulting survival being compatible with an additive effect. However, for Taxol-pretreated cells held for 6 h postirradiation, either in the absence or presence of Taxol, the resulting survival reproducibly demonstrated a marked less than additive effect. This was particularly prominent for cells held in the presence of Taxol. Subsequent experiments in which Taxol was added to cells immediately postirradiation again demonstrated a less than additive effect of the two modalities.


CONCLUSIONS
The results of this study are consistent with a dual mechanism of action involving Taxol-induced radiation resistance, possibly as a consequence of postirradiation holding in G2, and radiation-induced Taxol resistance through an as-yet-undefined mechanism.
Ingram
M L
ML
Department of Radiation Oncology, University of California Irvine, 92697, USA.
Redpath
J L
JL
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel