Effect of carbogen breathing on the pharmacodynamics of 5-fluorouracil in a murine colon carcinoma.
To determine whether carbogen breathing has an effect on 5-fluorouracil (5-FU) uptake, retention and metabolism in C38 murine colon tumours grown in C57Bl/6 mice, we used in vivo 19F nuclear magnetic resonance (NMR) spectroscopy. Eleven tumour-bearing mice were treated with 150 mg/kg of 5-FU given intraperitoneally (i.p.). Five mice received carbogen gas (95% O(2) and 5% CO(2)) for 9.5 min, starting 1 min before 5-FU administration. We found increased levels of 5-FU and its anabolites and catabolites by sequential ¿19F NMR spectroscopy in the group treated with 5-FU in combination with carbogen compared with the group treated with 5-FU alone. The maximum of normalised values of 5-FU and its metabolites, reached after carbogen breathing, was almost 2-fold higher than after treatment with 5-FU alone. Despite these increased concentrations no significant effect of carbogen on growth inhibition of the tumour by 5-FU was observed, which may be related to the size as well as the well vascularised and perfused conditions of the tumours studied.
Kamm
Y J
YJ
Department of Medical Oncology, University Hospital, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. y.kamm@onco.azn.nl
Heerschap
A
A
Wagener
D J
DJ
D000280:Administration, Inhalation; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D002245:Carbon Dioxide; C011700:carbogen; D010100:Oxygen; D005472:Fluorouracil