RELATIONSHIP BETWEEN SURVIVING FRACTIONS USING THE COLONY METHOD, THE LD50, AND THE GROWTH DELAY AFTER IRRADIATION OF HUMAN-MELANOMA CELLS GROWN AS MULTICELLULAR SPHEROIDS

Survival of human melanoma Na 11 cells after .gamma. irradiation was measured using 3 different endpoints: clonogenicity of single cells isolated from spheroids either before or after treatment, probability of cure by sterilization of 50% of the spheroids and growth delay which includes the overall late effect (cell cycle delay, repair, repopulation, etc.). No significant difference in radiosensitivity was found between single cells and cells from spheroids. A close relationship was found between the cell yield and the theoretical number of cells per spheroid. Cell size did not vary significantly with increase in spheroid volume. The LD50 was determined by probit analysis of cure data obtained from 978 individually followed spheroids and a survival curve was reconstituted. Good agreement was found between the LD50 survival curve and that from monodispersed cells. When growth delay was plotted against survival, a similar conclusion was reached but with somewhat less precision, indicating that other factors must contribute to regrowth. The multicellular spheroid culture, which permits multiendpoint evaluation of survival, should provide a valid assay of human tumor cell sensitivity to radiation and chemotherapeutic treatments.