MODULATION OF TUMOR HYPOXIA BY CONVENTIONAL CHEMOTHERAPEUTIC-AGENTS

Purpose: We have evaluated the capacity of a number of common cancer c hemotherapeutic drugs to modulate the oxygenation of human tumor xenog rafts growing in murine hosts. Methods and Materials: Considerable eff ort has been expended on developing methods to radiosensitize hypoxic cells, or to selectively kill them with appropriate chemicals. Another approach, suggested by our ongoing studies with spheroids in vitro, i s to modify tumor oxygenation by physiological means. The feasibility of this approach is illustrated in this article using human tumor xeno grafts in mice treated with doxorubicin or mitomycin C plus radiation. The therapeutic potential of the combination treatments has been asse ssed using fluorescence-activated cell sorting techniques to isolate a nd differentially study hypoxic vs. aerobic cell subpopulations from t he xenografts. Additionally, drug-induced changes in blood flow have b een quantified at the macroscopic level with laser Doppler flowmetry, and at the microregional level with image analysis techniques. Results : At doses which produced only modest amounts of tumor cell killing, d oxorubicin and mitomycin C markedly altered tumor blood flow in all tu mor types examined, and with all assays used. Conclusion: Common anti- cancer agents may find new use as blood flow modifiers for combined mo dality treatments, in addition to their conventional use as ''pure'' c ytotoxins.