Effect of paclitaxel (TAXOL) alone and in combination with radiation on the gastrointestinal mucosa

Journal Article · Sun Jul 30 04:00:00 EDT 1995 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/0360-3016(95)00037-Y· OSTI ID:539412

Mason, K A; Milas, L; Peters, L J ^[1]

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1. Univ. of Texas, Houston, TX (United States)

Paclitaxel is a potentially useful drug for augmenting the cytotoxic action of radiotherapy because it has independent cytotoxic activity against certain cancers and blocks cells in the radiosensitive mitotic phase of the cell cycle. However, all rapidly proliferating tissues, both normal and neoplastic, may be affected by this therapeutic strategy. The aim of this study was to define the in vivo response of rapidly dividing cells of the small bowel mucosa in mice to paclitaxel given alone and in combination with radiation. Paclitaxel blocked jejunal crypt cells in mitosis and induced apoptosis in a dose-dependent manner. Fractionating the paclitaxel dose over 1-4 days did not result in any greater accumulation of mitotically blocked cells than did a single dose. Mitosis peaked 2-4 h after paclitaxel and returned to near normal by 24 h. Apoptosis lagged several hours behind mitosis and peaked about 6 h later than mitosis. Despite these kinetic perturbations, there was little or no enhancement of radiation effect when single doses were delivered 2-4 h after paclitaxel administration. The maximum sensitizer enhancement ratio of 1.07 observed after a single paclitaxel dose of 40 mg/kg is consistent with independent crypt cell killing. Conversely, when radiation was given 24 h after paclitaxel, a significant protective effect of the drug (SER 0.89-0.92), most probably due to a regenerative overshoot induced by paclitaxel, was observed. Stem cells of the jejunal mucosa determining radiation response were not radiosensitized by paclitaxel with the drug concentrations and dose deliver schedules used, although additive cytotoxicity was observed with the highest drug dose. A radioprotective effect was observed when radiation was given 24 h after paclitaxel administration. 33 refs., 4 figs., 3 tabs.

• OSTI ID: 539412
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 32; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
ANTINEOPLASTIC DRUGS
BIOASSAY
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CELL CYCLE
CELL KILLING
CELL PROLIFERATION
CHEMOTHERAPY
COMBINED THERAPY
DOSE-RESPONSE RELATIONSHIPS
EVALUATION
FRACTIONATED IRRADIATION
GASTROINTESTINAL TRACT
MICE
MITOSIS
NEOPLASMS
RADIATION INJURIES
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RADIOTHERAPY
STEM CELLS
WHOLE-BODY IRRADIATION