The prostaglandin E1 analog, misoprostol, a normal tissue protector, does not protect four murine tumors in vivo from radiation injury.
The clinical development of radioprotectors, such as misoprostol, to protect normal tissue during cancer treatment must proceed with the assurance that tumors are not protected similarly or significantly. To provide data on this critical question, radiation-induced growth delay with or without the presence of misoprostol was measured in four murine tumors grown in the flanks of mice: the Lewis lung carcinoma, M-5076 ovarian sarcoma, FSA and NFSA. The effect of misoprostol on the tumor control dose (TCD50) of radiation was measured in FSA-bearing mice with or without prior treatment with the nonsteroidal anti-inflammatory agent, indomethacin. Misoprostol did not influence the in vivo growth of any of the four tumors, nor did it protect any of the tumors from radiation-induced growth delay. Likewise, there was no increase in the radiation TCD50 to treat the FSA in vivo in control or indomethacin-treated tumor-bearing mice. To measure any possible influence of tumor burden on the protective effect of misoprostol on normal tissue in mice, the protective effect of misoprostol on the survival of intestinal clonogenic cells was measured in M-5076-bearing mice and found to be the same as in non-tumor-bearing mice. These data suggest that misoprostol protects normal tissue in mice without protecting at least four experimental murine tumors. The data support the contention that misoprostol can achieve therapeutic gain by protecting normal tissues without protecting tumors.
Hanson
W R
WR
Loyola-Hines Department of Radiotherapy, Loyola University Chicago, Illinois, USA.
Zhen
W
W
Geng
L
L
Hunter
N
N
Milas
L
L
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008175:Lung Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D016595:Misoprostol / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012044:Regression Analysis; D012513:Sarcoma, Experimental / Q000473:pathology* / Q000532:radiotherapy
D011837:Radiation-Protective Agents; D016595:Misoprostol; D007213:Indomethacin