PJS Vol 135 No. 2, December 2006
Page 73-81
ISSN 0031-7683
Radioprotection of Intestinal Crypt Cells By Cox-Inhibitors
The regulation of tissue homeostasis in the gastrointestinal epithelium after epithelial injury focuses on the prostaglandins (PGs) as its major mediators. The two cyclooxygenase isoforms, Cox-1 and Cox-2, catalyze synthesis of PGs. Cox-1 is the predominant cyclooxygenase isoform found in the normal intestine. In contrast, Cox-2 is present at low levels in normal intestine but is elevated at sites of inflammation, and in adenomas and carcinomas. To study the effects of various commercially-available cox-inhibitors (Ketorolac: Cox-1 selective; Celecoxib: Cox-2 selective; and Indocid: Cox-1/2 non-selective), we determine mouse crypt epithelial cell fate after genotoxic injury with whole-body gamma-ray exposure at 15 Gy. Intestinal tissues of mice treated with Cox-2 inhibitors that showed invariable apoptotic event, however, have increased occurrence of regenerating cells. Our results suggest a potential application of Cox-2 selective inhibitors as radioprotective agent for normal cells after radiotherapy.
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