RSRl3,
2
3
4
5
-dimethylanilino)carbonyl)methyl)phenoxy] -2-methylpropionic acid, stabilizes deoxyhemoglobin and increases O2 delivery to normal muscle in C3H mice. The effect of RSRl3 on the hypoxic fraction of FSaII fibrosarcoma isotransplants in C3H mice was determined by measuring FSaII cell survival following radiation exposures. The results were evaluated by multivariate analysis. RSRl3 (300 mgkg) was administered i.p. 20 min prior to irradiation. In tumor growth delay experiments (n = 90), FSaII tumor growth was reduced by the combination of RSRl3 and radiation relative to radiation alone (P = 0.01 for a single exposure and P = 0.06 for multiple exposures). RSRl3 alone did not affect tumor growth. In clonogenic assay experiments (n = 196), tumors in mice were exposed to RSRl3 and either air or carbogen (95% 02, 5% C 0 2 ) breathing during single radiation exposures of up to 15 Gy, and FSaII cell survival was determined in vitro. FSaII cell survival was significantly (P < 0.0001) reduced in mice that were exposed to RSR13 and carbogen compared to mice exposed to RSRl3 and air, carbogen only, or air only. RSRl3 and radiation dose responses were also tested in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylformazan bromide assay, and 1 hr exposures of RSRl3 (concentrations up to 3 mM) & 3 Gy or 4.5 Gy did not affect FSAII cell proliferation. RSRl3 probably increases O2 delivery to and reduces the hypoxic fraction of FSaII tumors.