Hypoxyradiotherapy: lack of experimental evidence for a preferential radioprotective effect on normal versus tumor tissue as shown by direct oxygenation measurements in experimental sarcomas.
OBJECTIVE
In order to investigate possible pathophysiological mechanisms underlying the postulated preferential protective effect of hypoxia on normal tissue during radiotherapy, the impact of acute respiratory hypoxia (8.2% O2 + 91.8% N2) on tissue oxygenation was assessed.


METHODS
Tumor and normal tissue oxygenation was directly determined using O2-sensitive electrodes in two experimental rat tumors (DS and Yoshida sarcomas) and in the normal subcutis of the hind foot dorsum.


RESULTS
During respiratory hypoxia, arterial blood O2 tension (pO2), oxyhemoglobin saturation and mean arterial blood pressure decreased. Changes in the arterial blood gas status were accompanied by a reflex hyperventilation leading to hypocapnia and respiratory alkalosis. In the subcutis, tissue oxygenation worsened during acute hypoxia, with decreases in the mean and median pO2. Significant increases in the hypoxic fractions were, however, not seen. In tumor tissues, oxygenation also worsened upon hypoxic hypoxia with significant decreases in the mean and median pO2 and increases in the size of the hypoxic fractions for both sarcomas.


CONCLUSIONS
These results suggest that during respiratory hypoxia, radiobiologically relevant reductions in the oxygenation (and a subsequent selective radioprotection) of normal tissue may not be achieved. In addition, in the tumor models studied, a worsening of tumor oxygenation was seen which could result in an increased radioresistance.
Kelleher
D K
DK
Institute of Physiology and Pathophysiology, University of Mainz, Germany.
Thews
O
O
Vaupel
P
P
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure; D004195:Disease Models, Animal; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009368:Neoplasm Transplantation; D010101:Oxygen Consumption / Q000528:radiation effects*; D010108:Oxyhemoglobins / Q000378:metabolism; D018714:Radiotherapy, Adjuvant; D051381:Rats; D017207:Rats, Sprague-Dawley; D012513:Sarcoma, Experimental / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*
D010108:Oxyhemoglobins