EFFECT OF CARBON-MONOXIDE BREATHING ON HYPOXIA AND RADIATION RESPONSEIN THE SCCVII TUMOR IN-VIVO

Purpose: To study the influence of a clinically relevant concentration of carbon monoxide (CO) on tumor oxygenation and response to irradiat ion. Methods and Materials: The murine tumor model was the SCCVII squa mous cell carcinoma transplanted to the feet of C3H/Km mice. Results: Sixty minutes of breathing CO at 200 ppm resulted in a carboxyhemoglob in level of 15%. This resulted in a reduction in p50 (the oxygen parti al pressure at which hemoglobin is 50% saturated) to 78% of the contro l value, and a decrease in tumor blood perfusion to 73% of the control value. The combined effect of a decrease in effective hemoglobin and blood perfusion resulted in a reduction in tumor oxygen supply to 62% of the control value. In agreement with this, intratumoral PO2 measure ments showed a significant increase in tumor hypoxia, such that the pe rcentage of measurements with low pO(2) (less than or equal to 5 mmHg) increased from 33% to 62%. The fraction of clonogenic hypoxic cells, measured radiobiologically by paired cell survival curves, similarly i ncreased from 0.2% to 3.8%. Radiation sensitivity, evaluated from ill vivo-in vitro excision assay, was significantly decreased by CO breath ing with both single dose and fractionated irradiation. The observed e nhancement ratios for radiation given in 1, 4, 8, and 12 fractions wer e 0.71, 0.77, 0.83, and 0.71, respectively. Conclusion: The present SC CVII tumor data confirm the general experimental observation that CO b reathing significantly increases tumor hypoxia and reduces the effecti veness of ionizing irradiation.