Taxol-induced Pathological Findings in Rat Small Intestine

ABSTRACT

Taxol is an active chemotherapeutic agent against a variety of solid tumors and a potentially useful drug for augmenting the cytotoxic action of radiotherapy against certain cancers. Taxol blocks cells in the mitotic phase of cell cycle. The aim of this study was to define the in vivo response of rapidly dividing cells of the small intestinal mucosa to taxol. We studied the numbers of apoptotic and mitotic cells and the expression of bcl-2 and p53 in rat jejunal crypt cells at 1, 2, 4, 8, 12, 16, and 24 hours and 3 and 5 days after intraperitoneal injection of taxol. Mitosis peaked at 2 and 4 hours and 12 and 16 hours. Apoptosis peaked at 16 hours and returned to normal after five days. The glands in crypts showed marked distortion with atypical lining cells after three days, which returned to normal at 5 days. bcl-2 expression was markedly decreased at 8 to 24 hours and subnormally recovered after three to five days. p53 showed no significant changes throughout. The histopathological changes in small intestine due to taxol were transient with complete recovery. bcl-2 expression was inversely corresponded to numbers of apoptosis. The changes were p53 independent. Further studies to understand the conditions that maximize the cell-cycle modulating effects of taxol cl-may greatly enhance its anti-tumor effectiveness.