Quantitation of the response of human tumor spheroids to daily radiation exposures

Two human tumor lines, NB-100 neuroblastoma and C-32 melanoma, were grown as multicellular tumor spheroids (MTS) and exposed to daily doses of gamma rays, 5 days per week. It required daily doses of 200 rad to arrest the growth of the NB-100 MTS, while 350 rad per day was required to arrest the growth of the C-32 MTS. Calculation of the delay in time to grow 200 um beyond the original size yielded similar differences in radiation resistance. When the volume of the treated MTS was expressed as a fraction of their potential volume and plotted as a function of cumulative dose, there appeared to be little fraction size dependence over the range studied. This prediction was tested experimentally and confirmed: daily administration of two 100 rad doses separated by 4 hours to NB-100 MTS was only marginally less effective than a daily single dose of 200 rad. These data suggest that MTS may prove to be valuable tools in studying the response of human tumors to clinical exposure protocols, including hyperfractionation.