Effects of mitomycin C on the oxygenation and radiosensitivity of murine and human tumours in mice

Background and purpose: Mitomycin C was one of the first chemotherapeutic a gents to be shown to have preferential cytotoxicity toward hypoxic cells in vitro. Consequently, it has been used clinically with radiotherapy, and ha s stimulated considerable interest for analogue development. More recent st udies also suggested a possible role for the drug in enhancing tumour blood flow; we therefore undertook a comprehensive examination of mitomycin C as a potential radiosensitizer in murine and human rumours growing in mice. Materials and methods: Two dissimilar human tumour xenograft systems, SiHa and WiDr cells, were used as was the murine SCCVII line. Effects of mitomyc in C treatment on the regional and microregional blood flow in these tumour s was evaluated, and cell sorting based on dye perfusion techniques was use d to study the cytotoxicity of mitomycin C as a single agent or in combinat ion with radiation in the xenograft systems. Results: Contrary to our expectations, no preferential killing of less-well oxygenated tumour cells in situ was observed, nor were any consistent effe cts on tumour blood flow found. The inclusion of mitomycin C with radiation did, however, produce a modest increase in cell killing in the hypoxic sub populations of the xenograft system with the largest hypoxic fraction. Conclusions: Our results indicate that combined treatment with mitomycin C and radiation cannot be rationalized on the expectation of either complemen tary cytotoxicity of the modalities, or of drug-induced improvement in tumo ur oxygenation. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.