The effects of host carbogen (95% oxygen/5% carbon dioxide) breathing on metabolic characteristics of Morris hepatoma 9618a.
Characteristics of the tumour metabolic profile play a role in both the tumour-host interaction and in resistance to treatment. Because carbogen (95% oxygen/5% carbon dioxide) breathing can both increase sensitivity to radiation and improve chemotherapeutic efficacy, we have studied its effects on the metabolic characteristics of Morris hepatoma 9618a. Host carbogen breathing increased both arterial blood pCO2 and pO2, but decreased blood pH. A fourfold increase in tumour pO2 (measured polarographically) and a twofold increase in image intensity [measured by gradient recalled echo magnetic resonance (MR) imaging sensitive to changes in oxy/deoxyhaemoglobin] were observed. No changes were seen in blood flow measured by laser Doppler flowmetry. Tumour intracellular pH remained neutral, whereas extracellular pH decreased significantly (P < 0.01). Nucleoside triphosphate/inorganic phosphate (NTP/Pi), tissue and plasma glucose increased twofold and lactate decreased in both intra- and extracellular compartments, suggesting a change to a more oxidative metabolism. The improvement in energy status of the tumour was reflected in changes in tissue ions, including Na+, through ionic equilibria. The findings suggest that the metabolic profile of hepatoma 9618a is defined partly by intrinsic tumour properties caused by transformation and partly by tissue hypoxia, but that it can respond to environmental changes induced by carbogen with implications for improvements in therapeutic efficacy.
Stubbs
M
M
Cancer Research Campaign Biomedical Magnetic Resonance Research Group, Division of Biochemistry, St. George's Hospital Medical School, London, UK.
Robinson
S P
SP
Rodrigues
L M
LM
Parkins
C S
CS
Collingridge
D R
DR
Griffiths
J R
JR
D000280:Administration, Inhalation; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000097:blood; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D010100:Oxygen / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D010313:Partial Pressure; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011915:Rats, Inbred BUF
D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D019344:Lactic Acid; C011700:carbogen; D005947:Glucose; D010100:Oxygen