Middle dose rate irradiation in combination with carbogen inhalation selectively and more markedly increases the responses of SCCVII tumors

Abstract

Purpose : Carbogen increases the radiation response of tumors and reduced dose rate irradiation spares the damage of normal tissues. The purpose in this paper is to investigate the possibility of selective radiosensitization of tumors by reduced dose rate irradiation in combination with carbogen inhalation. Methods and Materials : SCCVII tumors in C3H/He mice were irradiated at middle dose rate (0.1 Gy/min) or high dose rate irradiation (3.0 Gy/min) in combination with carbogen inhalation. The mice were enclosed in a box with carbogen flushing at 1.0 1/min. The tumor response was measured by a cytokinesis block micronucleus assay. The effects on intestinal crypt cells and bone marrow cells were investigated by microcolony assay or Hendry's method, respectively. Results : The anti-tumor effect of middle dose rate irradiation was equal 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 intestinal crypt cells and bone marrow cells in comparison with high dose rate irradiation, and carbogen inhalation never enhanced the responses of these normal tissues in combination with middle dose rate irradiation. 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 those obtained with any other radiosensitizers, this combination has a potential as a new modality for improving the results of cancer radiotherapy.