16, 16-dimethyl prostaglandin E2 increases survival of murine intestinal stem cells when given before photon radiation

Abstract

A variety of prostaglandins (PG) protect the gastric and intestinal mucosa when given before damaging agents such as absolute ethanol, acidified taurocholate, boiling water, or nonsteroidal anti-inflammatory agents (NSAI). A synthetic prostaglandin, 16, 16-dimethyl PGE2, shown to be cytoprotective at physiologic levels to the above agents was given to mice 1 hr before or 15 min after 137Cs gamma (gamma) whole-body irradiation. The survival of intestinal stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased when 16, 16-dimethyl PGE2 was given before but not after 137Cs gamma irradiation. The maximum degree of 16, 16-dimethyl PGE2-induced radioprotection was seen when the drug was given 1 hr before irradiation. No radioprotection was seen when the interval between drug and irradiation was 3 hr or longer. When the time between 16, 16-dimethyl PGE2 and irradiation was kept at 1 hr, the degree of radioprotection was dependent on the PG drug dose. There was a steep rise in the number of surviving cells at low doses of PG. These results imply that tumors which secrete PGE2 may in part be protected from the lethal effects of ionizing photon radiation.