Response of cell subpopulations in spheroids to radiation-drug combinations.

Chinese hamster V79 cells grown as multicell spheroids were treated with radiation and/or selected antineoplastic drugs (5-fluorouracil, cisplatin, doxorubicin, mitomycin, and carmustine) administered at equitoxic levels in defined preirradiation and postirradiation sequences. Clonogenicity of the treated cells was determined, and the results from conventional assays were compared with those from cell-selection experiments, using a fluorescence-activated cell sorter, to determine the degree of interaction and regions of activity of the agents. Marked sequence-dependent differences in overall toxicity were observed; drug toxicity, spheroid reoxygenation, and direct sensitization appeared to be operative to a different extent with each drug and sequence. Maximal interaction between all drugs and radiation was, however, observed when drug exposure immediately preceded irradiation.