In vivo and in vitro radioprotective effects of the prostaglandin E1 analogue misoprostol in DNA repair-proficient and -deficient rodent cell systems.
The radioprotective effect of a stable prostaglandin E(1) analogue, misoprostol, was studied in cells from mice with severe combined immunodeficiency (SCID) and in normal cells using X-ray-induced chromosomal aberrations and/or cell killing as the end points. The results clearly show misoprostol-induced radioprotective effects in spermatocytes of the first meiotic division when analyzed for X-ray-induced chromosomal aberrations. The protective effect was independent of Trp53 (formerly known as p53) status. Since spermatocytes are relatively easy to isolate, this appears to be a suitable in vivo model that will allow biochemical studies of the mechanisms involved in radioprotection mediated by misoprostol. Using transfected CHO-K1 cells that stably express a PGE(2) receptor (CPE cells), significant radioprotection mediated by misoprostol from both chromosome breakage and cell death could be demonstrated under in vitro conditions. In addition, evidence was obtained indicating that the degree of radioprotection was dependent on the cell cycle and that S-phase cells were less responsive to misoprostol-mediated radioprotection. These results suggest that CPE cells may be a suitable in vitro model for further studies on the cellular pathways involved in radioprotection by misoprostol in particular and prostaglandins in general.
van Buul
P P
PP
Department of Radiation Genetics and Chemical Mutagenesis-MGC, Leiden University Medical Center, Sylvius Laboratory, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands.
van Duyn-Goedhart
A
A
Sankaranarayanan
K
K
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D002869:Chromosome Aberrations; D004260:DNA Repair; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D016595:Misoprostol / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D011837:Radiation-Protective Agents; D016159:Tumor Suppressor Protein p53; D016595:Misoprostol