Study of toxicity of Samarium-153-EDTMP in the treatment of painful skeletal metastasis. Final report for the period 15 December 1996 - 14 December 1997

Favourable characteristics of Sm-153 EDTMP make it an effective agent for use in the palliative treatment of metastatic bone pain. It has also been postulated that Sm-153 might have some tumoricidal effect. But until today its mechanism of action in the treatment of skeletal metastasis is not known. This experimental study has been designed to study the cellular and molecular changes occurring in the bone tumour cells (osteosarcoma of femur of wister rats) following irradiation with different doses of Sm-153 EDTMP. Experimental osteosarcorna tumour cells were harvested and treated with Sm-153 EDTMP over different periods of time ranging from 1-24 hours. Electron microscope, fluorescence microscope, MTI assay and 3HTdR release assay studies were conducted to observe for effects of radiation. Sm-153 EDTMP irradiation of bone tumour cells resulted in significant nuclear fragmentation, margination of condensed chromatin, marked pyknosis and increased formation of membrane bounded apoptotic bodies formation. The quantification analysis of fragmented DNA for bone tumour cells induced by Sm-153 EDTMP showed that the DNA fragmentation was enhanced with prolongation of irradiation time. The inhibition rate of proliferation of bone tumour cells as well as DNA fragmentation in bone tumour cells after irradiation with Sm-153 EDTMP increased significantly and progressively with prolongation of irradiation time, reaching levels of 63% and 78% respectively by 24 hours. (author)