MIDDLE DOSE-RATE IRRADIATION IN COMBINATION WITH CARBOGEN INHALATION SELECTIVELY AND MORE MARKEDLY INCREASES THE RESPONSES OF SCCVII TUMORS

Purpose: Carbogen increases the radiation response of tumors and reduc ed dose rate irradiation spares the damage of normal tissues. The purp ose in this paper is to investigate the possibility of selective radio sensitization of tumors by reduced dose rate irradiation in combinatio n with carbogen inhalation. Methods and Materials: SCCVII tumors in C3 H/He mice were irradiated at middle dose rate (0.1 Gy/min) or high dos e rate irradiation (3.0 Gy/min) in combination with carbogen inhalatio n. The mice were enclosed in a box with carbogen flushing at 1.0 l/min . The tumor response was measured by a cytokinesis block micronucleus assay. The effects on intestinal crypt cells and bone marrow cells wer e investigated by microcolony assay or Hendry's method, respectively. Results: The anti-tumor effect of middle dose rate irradiation was equ al to that of a high dose rate irradiation. Carbogen inhalation, more efficiently, increased the antitumor effect when combined with middle and high dose rate irradiation, and yielded enhancement ratios of 1.6 at around 2 Gy. Middle dose rate irradiation produced less damage on i ntestinal crypt cells and bone marrow cells in comparison with high do se rate irradiation, and carbogen inhalation never enhanced the respon ses of these normal tissues in combination with middle dose rate irrad iation. Dose modifying factors were 1.3-2.0. Conclusion: Since middle dose rate irradiation in combination with carbogen inhalation gave the therapeutic gain factors of 2.0-3.2, which were much larger than thos e obtained with any other radiosensitizers, this combination has a pot ential as a new modality for improving the results of cancer radiother apy.