The effect of hypoxia and hyperoxia on nucleoside triphosphate/inorganic phosphate, pO2 and radiation response in an experimental tumour model.
This study has evaluated the effect of breathing 100% oxygen, carbogen and carbon monoxide (at 660 p.p.m.) on the bioenergetic and oxygenation status and the radiation response of 200-mm3 C3H mammary carcinomas grown in the feet of CDF mice. Bioenergetic status was assessed by 31P magnetic resonance spectroscopy (MRS) using a 7-tesla spectrometer with both short (2 s) and long (6 s) pulse repetition times. Tumour partial pressure of oxygen (PO2) was measured with an Eppendorf polarographic electrode; the oxygenation parameters were the median pO2 and fraction of pO2 values < or = 2.5 mmHg. The radiation response was estimated using a tumour growth delay assay (time to grow three times treatment volume). Carbon monoxide breathing decreased tumour pO2 and compromised the radiation response, but the beta-nucleoside triphosphate (NTP)/Pi ratio was unchanged. Both carbogen and oxygen (100%) increased tumour pO2 and beta-NTP/Pi and enhanced the radiation response, the effects being similar under the two gassing conditions and dependent on the gas breathing time. Thus, in this tumour model, 31P-MRS can detect hyperoxic changes, but because cells can remain metabolically active even at low oxygen tensions the beta-NTP/Pi did not correlate with low tissue oxygenation. An analysis of variance showed that gas breathing time induced a significant systematic effect on beta-NTP/Pi, the MRS pulse repetition time had a significant effect on beta-NTP/Pi change under hypoxic but not under hyperoxic conditions and the type of gas that was inhaled had a significant effect on beta-NTP/Pi.
Nordsmark
M
M
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus C.
Maxwell
R J
RJ
Horsman
M R
MR
Bentzen
S M
SM
Overgaard
J
J
D000280:Administration, Inhalation; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage; D002248:Carbon Monoxide / Q000008:administration & dosage; D002455:Cell Division / Q000502:physiology; D004734:Energy Metabolism; D005260:Female; D018496:Hyperoxia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000196:embryology* / Q000532:radiotherapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D009711:Nucleotides / Q000378:metabolism*; D010100:Oxygen / Q000008:administration & dosage* / Q000378:metabolism; D010313:Partial Pressure; D010710:Phosphates / Q000378:metabolism*; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage
D009711:Nucleotides; D010710:Phosphates; D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D002248:Carbon Monoxide; C011700:carbogen; D010100:Oxygen