Prostaglandin-induced radioprotection of murine intestinal crypts and villi by a PGE diene analog (SC-44932) and a PGI analog (iloprost).
The aminothiols exemplified by WR-2721 are effective radioprotectors; however, their toxicity associated with hypotension, nausea, and emesis has limited their development for applications to medicine or in harzardous radiation environments.  There is a need for new radioprotectors that have fewer toxic side effects when given alone or combined with reduced amounts of thiols.  A variety of prostaglandins (PGs) have been shown to be radioprotective agents and some appear to have fewer toxic side effects than the aminothiols.  Iloprost, a stable PGI, analog protects the clonogenic epithelial cells of intestinal crypts but does not protect epithelial cells of the villi.  In contrast, an E-series omega chain diene analog designated SC-44932 protects epithelial cells of both crypts and villi.  When the two are combined, protection of the crypts is additive and the villi are protected to the same degree as when SC-44932 is given alone.  Since radioprotection for some PGs has been shown to be dependent upon receptors, we suggest that the pattern of radioprotection seen with these two analogs depend on the location of the respective receptors or on the ability of differentiated villus cells to respond to PGs.  By studying different analogs, we hope to identify mechanisms associated with PG-induced radioprotection and to identify the most protective PG analogs for applications of radioprotection.
Hanson
W R
WR
Loyola-Hines Department of Radiotherapy, Hines Veterans Affairs Hospital, Hines, IL 60141, USA.
Collins
P W
PW
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D004359:Drug Therapy, Combination; D016285:Iloprost / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D007583:Jejunum / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000517:prevention & control; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000627:therapeutic use*
D010975:Platelet Aggregation Inhibitors; D011459:Prostaglandins E, Synthetic; D011837:Radiation-Protective Agents; D016285:Iloprost