Effect of carbon monoxide breathing on hypoxia and radiation response in the SCCVII tumor in vivo.

ABSTRACT

PURPOSE: To study the influence of a clinically relevant concentration of carbon monoxide (CO) on tumor oxygenation and response to irradiation. METHODS AND MATERIALS The murine tumor model was the SCCVII squamous cell carcinoma transplanted to the feet of C3H/Km mice. RESULTS: Sixty minutes of breathing CO at 200 ppm resulted in a carboxyhemoglobin level of 15%. This resulted in a reduction in p50 (the oxygen partial pressure at which hemoglobin is 50% saturated) to 78% of the control 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 measurements showed a significant increase in tumor hypoxia, such that the percentage of measurements with low pO2 (< or = 5 mmHg) increased from 33% to 62%. The fraction of clonogenic hypoxic cells, measured radiobiologically by paired cell survival curves, similarly increased from 0.2% to 3.8%. Radiation sensitivity, evaluated from in vivo-in vitro excision assay, was significantly decreased by CO breathing with both single dose and fractionated irradiation. The observed enhancement ratios for radiation given in 1, 4, 8, and 12 fractions were 0.71, 0.77, 0.83, and 0.71, respectively. CONCLUSION: The present SCCVII tumor data confirm the general experimental observation that CO breathing significantly increases tumor hypoxia and reduces the effectiveness of ionizing irradiation.