TUMOR RADIOSENSITIZATION BY HIGH-OXYGEN-CONTENT GASES - INFLUENCE OF THE CARBON-DIOXIDE CONTENT OF THE INSPIRED GAS ON PO2, MICROCIRCULATORY FUNCTION AND RADIOSENSITIVITY

Purpose: To measure the effects of breathing high-oxygen-content gases , with a CO2 fraction of between 0 and 10%, on tumor radiosensitivity, blood flow and oxygenation. Methods and Materials: The murine sarcoma F was used, implanted subcutaneously (s.c.) in syngeneic CBA mice. We assessed the induced changes in tumour microregional blood flow and o xygenation using laser Doppler flowmetry, and pO(2) histography, respe ctively. Radiation response was determined using an in vivo-in vitro c lonogenic assay 18-20 h post treatment. Results: The results show that the level of radiosensitization achieved is dependent on both the CO2 content of the inspired gas and the duration of gas breathing. No rad iosensitization was evident following inhalation of 90% O-2 + 10% CO2. All other gases elicited radiosensitization; however, that achieved w ith 100% O-2 disappeared at the extended preirradiation breathing time of 45 min. At this time, radiosensitization was maintained for gases containing 1%, 2.5%, or 5% CO2. Changes in oxygenation, as measured by pO(2) electrodes, did indicate improved oxygenation status during inh alation of the gases. However, the time-course and extent of the chang es did not mirror accurately the changes in radiosensitization. All th e gases with a CO2 content of 2.5% or greater induced a 10-20% reducti on in microregional blood flow, with no change evident following inhal ation of 100% O-2 or 99% O-2 + 1% CO2. Conclusions: The data imply tha t the decreased radiosensitization seen at extended breathing times of oxygen is unrelated to blood flow changes. The fact that radiosensiti zation is seen with extended breathing times of gases containing 2.5% and 5% CO2, despite blood flow decreases, is indicative of other overr iding physiological changes, perhaps related to oxygen utilisation. Th e studies overall indicate that, at least in the tumour investigated, radiosensitization is not affected if the CO2 content of the inspired gas is reduced from 5% to 2.5%. or even 1%. Further evaluation of the radiosensitizing effects of such gas mixtures is now warranted. In add ition, comparison with recent studies of other tumour types, where car bogen has been shown to improve tumour blood flow, suggests that this may be a tumour-specific phenomenon. Based on these data, further effo rt is required to elucidate the physiological mechanisms that determin e these blood flow changes. (C) 1998 Elsevier Science Inc.