THE EFFECTS OF HOST CARBOGEN (95-PERCENT OXYGEN 5-PERCENT CARBON-DIOXIDE) BREATHING ON METABOLIC CHARACTERISTICS OF MORRIS-HEPATOMA-9618A

Characteristics of the tumour metabolic profile play a role in both th e tumour-host interaction and in resistance to treatment. Because carb ogen (95% oxygen/5% carbon dioxide) breathing can both increase sensit ivity to radiation and improve chemotherapeutic efficacy, we have stud ied its effects on the metabolic characteristics of Morris hepatoma 96 18a. Host carbogen breathing increased both arterial blood pCO(2) and pO(2), but decreased blood pH. A fourfold increase in tumour pO(2) (me asured polarographically) and a twofold increase in image intensity [m easured by gradient recalled echo magnetic resonance (MR) imaging sens itive to changes in oxy/deoxyhaemoglobin] were observed. No changes we re seen in blood flow measured by laser Doppler flowmetry. Tumour intr acellular pH remained neutral, whereas extracellular pH decreased sign ificantly (P < 0.01). Nucleoside triphosphate/inorganic phosphate (NTP /P-i), tissue and plasma glucose increased twofold and lactate decreas ed in both intra- and extracellular compartments, suggesting a change to a more oxidative metabolism. The improvement in energy status of th e tumour was reflected in changes in tissue ions, including Nat, throu gh ionic equilibria. The findings suggest that the metabolic profile o f hepatoma 9618a is defined partly by intrinsic tumour properties caus ed by transformation and partly by tissue hypoxia, but that it can res pond to environmental changes induced by carbogen with implications fo r improvements in therapeutic efficacy.