title: Biochemical responses in cultured cells following exposure to (89)SrCl(2): potential relevance to the mechanism of action in pain palliation.
abstract: (89)SrCl(2) is currently used as a systemic radioactive palliative treatment for painful osseous metastases associated with an osteoblastic reaction in bone. However, the biological mechanism by which (89)SrCl(2) mediates pain palliation remains unclear. In this study, attempts were made to elucidate the mechanisms by which (89)SrCl(2) might influence pain at these sites. Both the direct radiotoxic effects of (89)SrCl(2) on cell viability and its influence on cellular biosynthetic activity were investigated. The direct radiotoxic effects of (89)SrCl(2) and X-rays were compared using the prostate carcinoma cell line, PC-3. Comparable effects upon PC-3 cell viability were seen in response to exposure to an equivalent dose given by (89)SrCl(2) and X-rays (2 Gy). Experiments to investigate the indirect action of (89)SrCl(2) exposure employed the MC3T3-E1 cell line and focused on their production of Prostaglandin E(2) (PGE(2)) and interleukin-6 (IL-6). Exposure of the MC3T3-E1 cell line to (89)SrCl(2) resulted in an increased production of PGE(2) in a concentration-dependent manner. No increased PGE(2) production was seen by the MC3T3-E1 cells in response to X-ray exposure either in the presence or absence of SrCl(2). IL-6 was produced by the MC3T3-E1 cells in response to (89)SrCl(2) exposure via a PGE(2)-mediated pathway. This study demonstrates the release of potent biochemical modifiers of bone turnover in response to the systemically applied radiotherapeutic (89)SrCl(2). This strongly suggests the mechanism of pain palliation by (89)SrCl(2) is likely to result from a complex interaction of direct and indirect radiation-induced effects.
authors.affiliation: Amersham plc, Imaging Research and Development, Amersham Laboratories, White Lion Road, Amersham, Bucks HP7 9LL, UK.
authors.forename: J
authors.initials: J
authors.lastname: Davis
authors.forename: R J
authors.initials: RJ
authors.lastname: Pither
mesh_terms: D001859:Bone Neoplasms / Q000556:secondary; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D015232:Dinoprostone / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D010146:Pain / Q000517:prevention & control*; D010166:Palliative Care; D013324:Strontium / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects; D014965:X-Rays
chemical_list: D015850:Interleukin-6; C025700:strontium chloride; D015232:Dinoprostone; D013324:Strontium