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Misoprostol, a PGE1 analog, protects mice from fission-neutron injury
1Loyola-Hines Department of Radiotherapy, Loyola University, Hines, Illinois 60141.
Abstract:
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.
Insights
Prostaglandins like misoprostol protect against radiation injury by enhancing cell survival. However, this radioprotection mechanism does not appear to involve increased repair of sublethal radiation damage.
Area of Science:
- Radiation biology
- Molecular mechanisms of disease
Background:
- Eicosanoids are implicated in tissue injury and disease pathogenesis.
- Prostaglandins demonstrate protective effects against various physical and chemical agents, including radiation.
- The precise mechanism of prostaglandin-mediated radioprotection, particularly regarding DNA repair, remains largely unknown.
Purpose of the Study:
- To investigate the potential association between the repair of sublethal radiation damage and eicosanoid-induced radioprotection.
- To compare the protective effects of misoprostol (a prostaglandin E1 analog) and WR-2721, alone and in combination, against photon and neutron irradiation.
Main Methods:
- Experiments were designed to assess cell and animal survival following exposure to JANUS fission-spectrum neutrons and 137Cs gamma radiation.
- Mice were treated with misoprostol, WR-2721, or a combination of both prior to irradiation.
- Intestinal clonogenic cell survival and animal longevity were measured as endpoints.
Main Results:
- Both misoprostol and WR-2721, individually or combined, enhanced the survival of intestinal clonogenic cells and prolonged animal survival after JANUS neutron irradiation.
- The protective effects were qualitatively similar to those observed with 137Cs gamma radiation.
- The split-dose survival ratio for JANUS neutrons was 1, contrasting with approximately 6 for 137Cs gamma radiation.
Conclusions:
- Eicosanoid-induced radioprotection, as demonstrated by misoprostol, is unlikely to be explained by an enhancement of sublethal radiation damage repair.
- Further research is needed to elucidate the specific molecular pathways underlying prostaglandin-mediated radioprotection.