Misoprostol-induced radioprotection of Syrian hamster embryo cells in utero from cell death and oncogenic transformation.
Misoprostol, a PGE1 analog, is an effective radioprotector of murine intestine and hematopoietic and hair cell renewal systems. The radioprotective nature of misoprostol was extended to examine its ability to influence clonogenic cell survival and induction of oncogenic transformation in Syrian hamster embryo cells exposed to X rays in utero and assayed in vitro. Hamsters in their 12th day of pregnancy were injected subcutaneously with misoprostol, and 2 h later the pregnant hamsters were exposed to graded doses of X rays. Immediately after irradiation, hamsters were euthanized and embryonic tissue was explanted into culture dishes containing complete growth medium. After a 2-week incubation period, clonogenic cell survival and morphologically transformed foci were determined. Survival of misoprostol-treated SHE cells was increased and yielded a dose reduction factor of 1.5 compared to SHE cells treated with X rays alone. In contrast, radiation-induced oncogenic transformation of misoprostol-treated cells was reduced by a factor of 20 compared to cells treated with X rays alone. These studies suggest that misoprostol not only protects normal tissues in vivo from acute radiation injury, but also protects cells, to a large extent, from injury leading to transforming events.
St. Barnabas Medical Center, Department of Radiation Oncology, Livingston, New Jersey 07039.
R C
RC
Miller
P
P
LaNasa
W R
WR
Hanson
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D002999:Clone Cells; D006224:Cricetinae; D004307:Dose-Response Relationship, Radiation; D004622:Embryo, Mammalian / Q000187:drug effects / Q000528:radiation effects*; D005260:Female; D008647:Mesocricetus; D016595:Misoprostol / Q000494:pharmacology*; D011247:Pregnancy; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014965:X-Rays
D011837:Radiation-Protective Agents; D016595:Misoprostol