Differential radioprotective effects of misoprostol in DNA repair-proficient and -deficient or radiosensitive cell systems.
The protective effects of misoprostol (MP), an analogue of prostaglandin E1, on X-ray-induced chromosomal aberrations, were studied in normal or mutant Chinese hamster cell lines grown as spheroids in vitro and on cell-killing in stem-cell spermatogonia of a mutant (acid) mouse strain or its wild-type. The mutant hamster cell lines chosen for this purpose are known to be either hypersensitive to the killing effects of X-rays and/or deficient in the repair of DNA double-strand breaks. The scid mice are deficient in the repair of DNA double-strand breaks. The results show that MP manifests varying degrees of radioprotection in all these systems, but the magnitude of these effects in the mutants is markedly reduced compared to their respective wild-type counterparts. These findings suggest a link between ionizing radiation sensitivity, DNA double-strand break repair capability and MP-mediated radioprotection.
van Buul
P P
PP
Department of Radiation Genetics and Chemical Mutagenesis-MGC, Leiden University, Sylvius Laboratory, The Netherlands.
van Duyn-Goedhart
A
A
de Rooij
D G
DG
Sankaranarayanan
K
K
D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000528:radiation effects; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000528:radiation effects*; D006224:Cricetinae; D004260:DNA Repair / Q000187:drug effects*; D004307:Dose-Response Relationship, Radiation; D008297:Male; D051379:Mice; D016513:Mice, SCID; D016595:Misoprostol / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013093:Spermatogonia / Q000528:radiation effects; D014965:X-Rays
D011837:Radiation-Protective Agents; D016595:Misoprostol