16,16-Dimethyl prostaglandin E2 induces radioprotection in murine intestinal and hematopoietic stem cells.
Exogenous prostaglandins (PGs) have been shown to protect gastrointestinal mucosa, liver, and pancreas from several injurious agents, including the PG inhibitor, indomethacin. Previous studies from this laboratory showed exogenous administration of 16,16-dimethyl (dm) PGE2 also protected mouse intestinal stem cells from radiation injury. The present study extended that observation and demonstrated that PGs given to B6D2F1 mice 1 hr before irradiation increased the shoulder of the intestinal clonogenic cell survival curve. The D0 increased from 1.10 + 0.09 to 1.58 + 0.10 Gy. PGs increased the LD50/6 from 16.3 + 0.41 (95% confidence limits) in controls to 20.25 + 0.55 Gy. The 16,16-dm PGE2 increased the hematopoietic CFU-S survival in a qualitatively similar way; the extrapolation number (n) was increased from 1.03 (0.89-1.20) to 1.40 (1.27-1.54) and the D0 increased from 0.92 (0.87-0.98) to 1.14 (1.10-1.19) Gy. A large number of human tumors secrete a variety of PGs. Our results suggest that those tumors may be, in part, protected from radiation injury.
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002588:Cesium Radioisotopes; D003037:Cobalt Radioisotopes; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects*; D007422:Intestines / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D051379:Mice; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects / Q000528:radiation effects
D002588:Cesium Radioisotopes; D003037:Cobalt Radioisotopes; D011459:Prostaglandins E, Synthetic; D011837:Radiation-Protective Agents; D015064:16,16-Dimethylprostaglandin E2