Murine intestinal crypt survival after combined taxol plus radiation exposure.
Taxol is active against a number of cancers, some of which are also radiosensitive. The role of combined Taxol and radiotherapy has not been established. A theoretical benefit exists, however, due to the G2/M phase specificity of Taxol, and radiation-sensitizing effects have been observed in vitro. This study focused on the combined Taxol/radiation effect on murine intestinal epithelium. HA/ICR random-bred male mice were used to examine the temporal effect of injecting Taxol (40 mg/kg) before and after irradiation (12.5 Gy). The microcolony assay was used to determine the effect of single and combined modalities. Control groups consisted of no treatment, drug solvent only (Cremophor/ethanol/saline), radiation only, and Taxol only. A complete radiation dose-response study of treatment with and without Taxol was performed 12 hr after injection. Preirradiation Taxol appears not to enhance intestinal cell killing, and may even offer some protection when injected at 4 hr prior to irradiation. Postirradiation Taxol was found to enhance radiation response most dramatically at times greater than 12 hr. Dose-response data appeared to confirm the increased radiation effect of combined treatment. In conclusion, Taxol administered prior to irradiation results in either no sensitization or possible protection of the normal tissue response. Postirradiation Taxol appears to sensitize intestinal crypts when injected at least 12 hr after gamma irradiation. These data suggest that care should be exercised when using Taxol after irradiation.
Department of Obstetrics, Gynecologic and Reproductive Sciences, University of California/Mount Zion Cancer Center, San Francisco 94120, USA.
S L
SL
Lojun
C P
CP
Sigdestad
A M
AM
Connor
W J
WJ
Spanos
J R
JR
Bosscher
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D007583:Jejunum / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel