Experimental induction of rhabdomyosarcoma in mice with fractionated dosesof beta-irradiation

Repeated doses of beta-radiation in the mouse skin model have been reported to produce carcinomas and sarcomas with equal frequency. Among sarcomas, f ibrosarcomas and osteosarcomas have been the pre:dominant reported histolog ies. In this report we describe the beta-radiation induction of rhabdomyosa rcoma (RMS), a histology previously undescribed with tumor induction protoc ols using ionizing radiation in an animal model. Radiation-induced RMS is o ften seen as a secondary tumor following therapeutic irradiation for retino blastoma in children. In our experiment the backs of 50 CD-1 mice were irra diated 3 times weekly for 35 weeks using a Sr-90 source. The initial dose w as 5.5 Gy/application, which was later reduced to 3 Gy after 15 weeks due t o severe skin reactions. In all, 27 skin and subcutaneous tumors were seen and collected. Of 12 sarcomas seen, 9 had a rhabdoid histology; cell lines from 3 such tumors as well as a squamous-cell carcinoma (SCC) and a maligna nt fibrous histiocytoma (MFH) were established. Immunohistochemical analysi s of their parent tumors showed that the rhabdoid tumors expressed desmin, which established the diagnosis of RMS. Two-dimensional gel electrophoresis and Western analysis of insoluble protein extracts confirmed that the cell lines from RMS tumors expressed desmin. A screen for molecular alterations identified a mutant p53 phenotype for RMS and MFH cell lines. These radiat ion-induced RMS cell lines provide a unique opportunity to study the molecu lar biology of this tumor in an animal model and will help provide insight into the mechanisms of radiation-induced RMS in humans.