Chemosensitivity Testing in V79 Spheroids: Drug Delivery and Cellular Microenvironment 1,2

ABSTRACT-Chinese hamster V79 multicell spheroids growing in tissue culture exhibit many of the same properties as solid tumors outgrowing their blood supply, including the spontaneous devel-opment of both noncycling and hypoxic cell populations expected to be resistant to many chemotherapeutic agents. Cell-sorting techniques were used to select cells as a function of their position (depth) within the spheroid to test this prediction. "Sensitivity pro-files " of cells from various regions within spheroids after treatment with doxorubicin, bleomycin, 5-fluorouracil, carmustine, cisplatin, chlorambucil, and mitomycin are presented. Additionally, expo-sure of preseparated cells was used to distinguish inherent sensi-tivity from environmental or locational factors. For these drugs, penetration was a problem only for doxorubicin; in contrast, the microenvironment in the intact spheroid had a much greater influ-ence on cell sensitivity.-JNCI 1986; 77:247-252