Radiation response of human melanoma multicellular spheroids measured as single cell survival, growth delay, and spheroid cure: comparisons with the parent tumor xenograft.

The radiation response of multicellular spheroids, initiated from a human melanoma xenograft (E.E.) propagated in athymic mice, was studied using cell survival, growth delay, and spheroid cure as endpoints. The relationship between these endpoints was analyzed, and the radiation response of the spheroids was compared with the parent xenograft. At irradiation, the spheroids were 100 +/- 5 micron in diameter and did not contain radiobiologically hypoxic cells. Growth delay of the spheroids mainly depended on the fraction of surviving cells as measured in soft agar, that is, there was a good correlation between these two endpoints. Moreover, Do-values calculated from spheroid cure curves were similar to those of the cell survival curves measured in soft agar. However, the number of stem cells per spheroid, calculated from SCD50-values (the doses required to cure 50% of the spheroids), was at least a factor of seven lower than the clonogenicity of cells from disaggregated spheroids would indicate. The cellular radiosensitivity of the spheroids was similar to the parent xenograft. An intercellular contact effect was not found for the spheroids, in agreement with observations from studies of xenografted tumors. Moreover, specific growth delays, as well as Do-values calculated from cure curves were similar for spheroids and tumors when the data for the latter were corrected for the presence of hypoxic cells. The high degree of conformity in the results indicates that multicellular spheroids and xenografted tumors may complement one another in studies of human tumor radiobiology.