THE EFFECT OF HYPOXIA AND HYPEROXIA ON NUCLEOSIDE TRIPHOSPHATE INORGANIC-PHOSPHATE, PO(2) AND RADIATION RESPONSE IN AN EXPERIMENTAL TUMOR-MODEL

This study has evaluated the effect of breathing 100% oxygen, carbogen and carbon monoxide (at 660 p.p.m.) on the bioenergetic and oxygenati on status and the radiation response of 200-mm(3) C3H mammary carcinom as grown in the feet of CDF mice. Bioenergetic status was assessed by P-31 magnetic resonance spectroscopy (MRS) using a 7-tesla spectromete r with both short (2 s) and long (6 s) pulse repetition times. Tumour partial pressure of oxygen (pO(2)) was measured with an Eppendorf pola rographic electrode; the oxygenation parameters were the median pO(2) and fraction of pO(2) values less than or equal to 2.5 mmHg. The radia tion response was estimated using a tumour growth delay assay (time to grow three times treatment volume). Carbon monoxide breathing decreas ed tumour pO(2) and compromised the radiation response, but the beta-n ucleoside triphosphate (NTP)/P-i ratio was unchanged. Both carbogen an d oxygen (100%) increased tumour pO(2) and beta-NTP/P-i and enhanced t he radiation response, the effects being similar under the two gassing conditions and dependent on the gas breathing time, Thus, in this tum our model, P-31-MRS can detect hyperoxic changes, but because cells ca n remain metabolically active even at low oxygen tensions the beta-NTP /P-i did not correlate with low tissue oxygenation. An analysis of var iance showed that gas breathing time induced a significant systematic effect on beta-NTP/P-i, the MRS pulse repetition time had a significan t effect on beta-NTP/P-i change under hypoxic but not under hyperoxic conditions and the type of gas that was inhaled had a significant effe ct on beta-NTP/P-i.