Misoprostol, a PGE1 analog, protects mice from fission-neutron injury.
The eicosanoids are associated with pathophysiological events of tissue injury linked to a large number of diseases. In contrast, prostaglandins have been found to protect tissues from injuries sustained by exposure to a variety of physical and chemical agents including radiation. Little is known about the mechanism of protection by prostaglandins; however, some evidence suggests that the eicosanoids may influence the repair of DNA lesions that would influence cell or animal survival after irradiation. To investigate an association between repair of sublethal radiation damage and eicosanoid-induced radioprotection, experiments were designed to study similarities and differences in protection by misoprostol (a radioprotective PGE1 analog), WR-2721, or the combination of both, before photon or neutron injury. Misoprostol alone, WR-2721 alone, or the combination of the two increased survival of intestinal clonogenic cells and animal survival following exposure to JANUS fission-spectrum neutrons in a way similar qualitatively to protection by these same treatments from the effects of 137Cs gamma radiation. The split-dose survival ratio for JANUS neutrons is 1, whereas the ratio for 137Cs gamma radiation is about 6. Since misoprostol, alone or with WR-2721, both protected intestinal clonogenic cells and increased animal longevity following JANUS neutron irradiation, it is unlikely that a prostaglandin-induced increase in sublethal damage repair can explain the observed eicosanoid-induced radioprotection.
Hanson
W R
WR
Loyola-Hines Department of Radiotherapy, Loyola University, Hines, Illinois 60141.
Grdina
D J
DJ
D004999:Amifostine / Q000627:therapeutic use; D000818:Animals; D004359:Drug Therapy, Combination; D008297:Male; D051379:Mice; D016595:Misoprostol / Q000627:therapeutic use*; D009502:Neutrons; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*
D011837:Radiation-Protective Agents; D016595:Misoprostol; D004999:Amifostine