Sensitivity of rodent osteosarcoma clones to platinum-containing phosphonic acid complexes in vitro.

Osteosarcoma treatment still is unsatisfactory owing to the development of metastases. This situation causes many problems for the patients as well as the clinicians. Tumor heterogeneity is made responsible for the development of cell lines resistant to chemotherapy. As the transplantable osteosarcoma of the rat resembles the human metastasizing osteosarcoma, studies on clones of this tumor were started. The following compounds were investigated: AMDP, cis-diammine[nitrilotris-(methylphosphonato)(2-)-O1,N1]plati num II; DADP, cis-cyclohexane-1,2-diamine[nitrilotris(methylphosphonato)(2 -)-O1,N1]- platinum II; IMD, cis-diammine[imino-bis(methylphosphonato)(2-)-O1,N1]platinum II; DIMD, cis-cyclohexane-1,2-diamine[iminobis(methylphosphonato) (2-)-O1,N1]platinum II. In vitro assays were performed with cell lines derived from a lung metastasis with the limited-dilution method. The clones varied in modal chromosome number, growth kinetics and tumorigenicity. AMDP was the most potent compound in all three clones resulting in a concentration- and time-dependent effect while IMD was somewhat less active. The diamminocyclohexane derivatives were considerably less effective, inhibiting cell growth especially in clone C10. In contrast, clone C36 was more sensitive than C25 and did not recover within the observation period of 5 days. Viability was reduced significantly only in C10, when treated with AMDP. Differences between the clones and the various compounds in inhibiting cell growth could be observed. Therefore, further experiments on the heterogeneity and sensitivity of these cell lines seem promising.