Effect of the Paclitaxel and Radiation on the Large Bowel Mucosa of the Rat

Lee, Kyung Ja

Abstract

PURPOSE
Paclitaxel is a chemotherapeutic agent with a potent microtubule stabilizing activity that arrests mitosis at G2-M phase of cell cycle which is the most radiosensitive period. Therefore paclitaxel is considered as a cell cycle-specific radiosensitizer. This study investigates the effect of paclitaxel on the radiation response of the normal large bowel mucosa of the rat.
MATERIALS AND METHODS
The rats were divided into the three groups i.e., single intraperitoneal infusion of paclitaxel (10 mg/kg), a single fraction of irradiation (8 Gy, x-ray) to the whole abdomen, and a combination of irradiation (8 Gy, x-ray) given 24 hours after paclitaxel infusion. The histological changes as well as kinetics of mitotic arrest and apoptosis were evaluated on the large bowel mucosa at 6 hours, 1 day, 3 days and 5 days after treatment with paclitaxel alone, radiation alone and combination of paclitaxel and radiation.
RESULTS
The incidence of the mitotic arrest was not increased by paclitaxel infusion. The apoptosis appeared in 24 hours after paclitaxel infusion, and the histopathologic changes such as vesiculation, atypia and reduction of the goblet cell of the mucosa of the large bowel were demonstrated during the period from 6 hours to 3 days after, and returned to normal in 5 days after paclitaxel infusion. In irradiated group, the apoptosis was increased in 6 and 24 hours after irradiation, and the histopathologic changes of the mucosa were appeared in 24 hours and markedly increased in 3 days and returned to normal in 5 days. In combined group of irradiation and paclitaxel infusion, the apoptosis was appeared in 3 days and the histopathologic changes appeared during the period from 6 hours to 3 days after infusion. On the basis of the incidence of apoptosis and the degree of the histopathologic changes of the large bowel mucosa, there seemed to be additive effect by paclitaxel on radiation rather than sensitizing effect.
CONCLUSION
The histopathological changes of large bowel mucosa in combined group compared to radiation alone group suggested an additive effect of paclitaxel on radiation response in the large bowel of rat.