Modification of the radiocurability of a syngeneic murine squamous carcinoma by its site of growth, by electron-affinic drugs, and by ICRF 159.

A series of TCD50 experiments using a spontaneously arising, syngeneically transplated, murine squamous carcinoma is reported. Tumours implanted intradermally and irradiated while they remained superficial had a small but nonetheless cure-limiting hypoxic fraction of cells (TCD50 3,324-4,257 rad). The hypoxic fraction increased dramatically when these tumours invaded the subcutaneous tissues, or when tumours were implanted subcutaneously (TCD50 greater than 5,544 rad). Pre-treatment of mice with the electron-affinic drug Ro-07-0582 at a dose of 1 mg/g i.p. 20-30 minutes before irradiation effectively eliminated the hypoxic element from superficaial tumours (TCD50 1.862 rad). The same drug at a dose of 0-25 mg/g reduced the TCD50 for superficial tumours by a factor of 1-87 (3,986-2,134 rad), while another electron affinic drug, metronidazole, given at a dose of 0-25 mg/g reduced the TCD50 by a factor of 1-28 (4,257-3,337 rad). Treatment of mice with the drug ICRF 159, 30 mug/g daily from the time of tumour cell injection until the day of irradiation, reduced the TCD50 in unclamped tumours by less than 1-19. However, a commensurate reduction of TCD50 in clamped tumours suggested that improved tumour vascularization could not explain fully the drug's "radiosensitizing" action. The unique single radiation dose curability of most human skin cancers is discussed in the light of the experimental results, and the possible clinical implication of an increase in hypoxic fraction with tumour invasion is raised.