Therapeutic gain factors (TGFs) have been determined for three spontaneous tumors of the C3H mouse treated by photons + normobaric oxygen (${\rm O}_{2}1$ ATA), photons + hyperbaric oxygen ( O2 3 ATA), photons + misonidazole, or fast neutrons. The tumors were early generation isotransplants of spontaneous tumors: MCaIV, a mammary carcinoma; FSaII, a fibrosarcoma; and SCCVII, a squamous cell carcinoma. The tumors, transplanted to the right leg, were 6 mm at start of treatment. Normal tissue responses studied were acute reaction of normal skin (all treatment modalities) and LD50 following irradiation of the upper abdomen (in test of photons + O2 at 1 or 3 ATA). Thus both the tumor and normal tissues would be classified as "acute responding." All subject tissues were at ≃34.5-35°C at irradiation. Treatments were based on d(25)Be or p(43)Be fast neutron beams,60 Co and137 Cs photon beams. Treatments were given in 5 or 15 equal doses in 5 days. For photon treatments, TGFs ($\text{air}/{\rm O}_{2}$ 3 ATA) were substantially and significantly larger than 1 for all three tumor systems treated at small or large doses per fraction when related to skin or abdominal tissue responses. The TGFs ($\text{air}/{\rm O}_{2}$ 1 ATA) were > 1 at small doses per fraction for MCaIV and FSaII for skin as the normal tissue; the TGFs for all three tumors and at all doses per fraction would be > 1 when related to upper abdominal tissues. TGFs ( O2 1${\rm ATA}/{\rm O}_{2}$ 3 ATA) for photon irradiation > 1 were found only for SCCVII and that obtained for both large and small doses per fraction. Misonidazole achieved impressive TGFs (air/air + miso or$\text{air}/{\rm O}_{2}$ 1 ATA + miso); the drug was tested only at 10-12 Gy/fraction and relative to skin. RBEs (FN) for the three tumors were lower at 1.5-2 Gy(FN)/fraction than at 5-6 Gy(FN)/fraction, i.e. the opposite to that reported for normal tissue (RBE increases with decreasing dose per fraction). A TGF (relative to skin reaction) > 1 for fast neutron therapy was found only for SCCVII when treated at large doses/fraction; this was true for air or O2 1 ATA conditions.

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