Addition of a hypoxic cell selective cytotoxic agent (mitomycin C or porfiromycin) to Fluosol-DA/carbogen/radiation

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
S A HoldenB A Teicher

Abstract

In an effort to develop effective combination treatments for use with radiation against solid tumors, the cytotoxic effects of the addition of mitomycin C or porfiromycin on treatment with Fluosol-DA/carbogen (95% O2/5% CO2) breathing and radiation in the FSaIIC tumor system were studied. In vitro mitomycin C and porfiromycin were both preferentially cytotoxic toward hypoxic FSaIIC cells. After in vivo exposure, however, the cytotoxicity of mitomycin C toward single cell tumor suspensions obtained from whole tumors was exponential over the dose range studied, but for porfiromycin a plateau in cell killing was observed. With Fluosol-DA/carbogen breathing and single dose radiation, addition of either mitomycin C or porfiromycin increased the tumor cell kill achieved at 5 Gy by approximately 1.2 and 1.0 logs, respectively. Less effect was seen with addition of the drugs at the 10 and 15 Gy radiation doses. In tumor growth delay experiments, the addition of either mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation resulted in primarily an additive increase in tumor growth delay. The survival of Hoechst 33342 dye-selected tumor cell subpopulations indicated that Fluosol-DA/carbogen breathing increased the cyt...Continue Reading

References

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Citations

Jun 1, 1994·Cancer Metastasis Reviews·B A Teicher
Jan 1, 1993·Journal of Cancer Research and Clinical Oncology·B A TeicherK Menon
Oct 1, 1993·Cancer Treatment Reviews·S M SagarJ E Aldrich
Jan 1, 1992·Biomaterials, Artificial Cells, and Immobilization Biotechnology : Official Journal of the International Society for Artificial Cells and Immobilization Biotechnology·B A Teicher
Oct 1, 1991·International Journal of Radiation Biology·I LeeS H Levitt

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