Comparison of in vivo murine intestinal radiation protection by E-prostaglandins

The gastrointestinal cell renewal system is sensitive to injury by ionizing radiation. Natural prostaglandins (PGs) and their analogs have been shown to protect intestinal clonogenic cells (stem cells) in vivo from radiation injury. To further investigate structure and activity relationship in PGs as radiation protectors, studies were done with four E-series PGs: E1, E2, 16,16-dimethyl (dm) PGE2, and 15-deoxy, 16-methyl, 16-hydroxy PGE1 (misoprostol). No protection was seen with PGE1 at doses ranging from 1-100 ug/mouse given from 15 min to 3 hrs before 15.0 Gy137Cs. In contrast, the other three E-series PGs increased intestinal clonogenic cell survival when given 15 min before irradiation. The optimum pre-irradiation time of PG administration was 1 hr for PGE2 and 16,16-dm PGE2 and 2 hrs for misoprostol. The degree of maximum radiation protection was markedly different among the four PGs. PGE2 increased survival to 200% of control values and 16,16-dm PGE2 increased survival to about 400% of controls. The greatest radioprotection was seen with misoprostol, which increased survival to 600% of control. These results suggest that molecular alterations in the side chains of PGs change the efficiency of PG-induced radiation protection. The highest protection to date has been observed with misoprostol. This important finding warrants clinical investigation in patients subjected to radiotherapy.