GROWTH-RATE, LABELING INDEX, AND RADIATION SURVIVAL OF CELLS GROWN INTHE MATRIGEL THREAD IN-VITRO TUMOR-MODEL

Six rodent cell lines (36B10 rat glioma cells, 9L rat gliosarcoma cell s, V79 Chinese hamster lung fibroblasts, EMT6/UW and EMT6/Ro mouse mam mary sarcoma cells, and RIF-1 mouse fibrosarcoma cells) were tested fo r growth in cylindrical threads of Matrigel. These cells grew in the t hreads with doubling times of 17-23 h, reaching maximum cell densities on the order of 10(8) cells/ml. Histological sections of these thread s showed a heterogeneous cell distribution: cells grew to confluence a t the thread surface and at somewhat lower cell densities in the threa d core. [H-3]thymidine labeling index and radiation sensitivity were m easured for 9L and EMT6/UW cells in Matrigel threads. For both cell ty pes, the labeling index in Matrigel was lower than observed in cell mo nolayers, with higher labeling indexes at the thread periphery than in the thread core. When these threads were grown in stirred medium, low er thread diameters, higher cell yields per thread, and higher labelin g indices were obtained. EMT6 cell monolayers coated with Matrigel wer e less radiosensitive than cells in uncoated monolayers. This protecti ve effect was eliminated by irradiating in the presence of 1 mg/ml mis onidazole. EMT6 cells consume nearly three times as much oxygen (mole/ cm(3)-sec) as do 9L cells, which are equally radiosensitive in monolay ers with or without a Matrigel coating. The radiation sensitivity of E MT6/UW cells in Matrigel threads was similar to that for monolayers of plateau phase cells, whereas for 9L cells, the response in threads wa s more similar to exponentially growing cells. We conclude that Matrig el threads provide an alternative in vitro model for studying the radi ation response of cells in a three-dimensional geometry.