THE PROSTAGLANDIN E(1) ANALOG, MISOPROSTOL, A NORMAL TISSUE PROTECTOR, DOES NOT PROTECT 4 MURINE TUMORS IN-VIVO FROM RADIATION-INJURY

The clinical development of radioprotectors, such as misoprostol, to p rotect normal tissue during cancer treatment must proceed with the ass urance that tumors are not protected similarly or significantly. To pr ovide data on this critical question, radiation-induced growth delay w ith 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 wit h or without prior treatment with the nonsteroidal anti-inflammatory a gent, indomethacin. Misoprostol did not influence the in vivo growth o f any of the four tumors, nor did it protect any of the tumors from ra diation-induced growth delay. Likewise, there was no increase in the r adiation TCD50 to treat the FSA in vivo in control or indomethacin-tre ated tumor-bearing mice. To measure any possible influence of tumor bu rden on the protective effect of misoprostol on normal tissue in mice, the protective effect of misoprostol on the survival of intestinal cl onogenic cells was measured in M-5076-bearing mice and found to be the same as in non-tumor-bearing mice. These data suggest that misoprosto l protects normal tissue in mice without protecting at least four expe rimental murine tumors. The data support the contention that misoprost ol can achieve therapeutic gain by protecting normal tissues without p rotecting tumors. (C) 1995 by Radiation Research Society