Increase in radioresponse of murine tumors by treatment with indomethacin.

Abstract

Indomethacin, an inhibitor of prostaglandin (PG) synthesis, was investigated for its ability to increase radioresponse of two fibrosarcomas, FSA and NFSA, in C3Hf/Kam mice. In addition, the effect of indomethacin on radioresponse of hematopoietic tissue, jejunum, hair follicles, and tissues involved in the development of radiation-induced leg contractures was determined. Indomethacin greatly increased radioresponse of 8-mm tumors, as assessed by both tumor growth delay and TCD50 assays. Enhancement factors for tumor growth delay and tumor radiocurability (TCD50) were 1.55 and 1.39, respectively, for FSA, and 1.4 and 1.26, respectively, for NFSA tumors. Of four normal tissues assessed, two (hair follicles and tissues responsible for development of leg contractures) showed no change in radioresponse after treatment with indomethacin, one (hematopoietic tissue) exhibited radioprotection, and one (jejunum) exhibited slight radiosensitization (enhancement factor, 1.12). Therefore, indomethacin significantly augmented tumor radiocurability but had minimal effect on radioresponse of some normal tissues.