AJP - Regulatory, Integrative and Comparative Physiology, Vol 244, Issue 1 84-R92, Copyright © 1983 by American Physiological Society
Incomplete free fatty acid oxidation by ascites tumor cells under low oxygen tension
M. Ookhtens and N. Baker
We tried to understand why our earlier estimates of fatty acid (FA)
oxidation rates under the nearly anaerobic state of the Ehrlich ascites
tumor (EAT) in vivo were even greater than those found in vitro under
aerobic conditions. Using tracers [1-14C]linoleate, [1-14C]-, and
[9,10-3H]palmitate, and NaH14CO3, we estimated essential and nonessential
FA oxidation rates to CO2 + H2O by EAT in living mice and in vitro under
aerobic and anaerobic conditions. Sequestration of intraperitoneally
(ip)-injected 14C-FFA allowed a selective labeling of the tumor versus the
host; thus, breath 14CO2 could be used to estimate the maximum rate of FA
oxidation in vivo by the tumor. Initially, we measured breath 14CO2
following NaH14CO3 injections and developed a multicompartmental model to
simulate the tumor-host HCO-3-CO2 system. This model was integrated with
our earlier model for tumor FA turnover. The integrated model was fitted to
breath 14CO2 data from mice injected ip with 14C-FFA to compute tumor FA
oxidation rates. Both essential and nonessential FA were oxidized to CO2 at
similar rates. The maximum rate of total FA oxidation to CO2 was 5-6 nmol
FA X min-1 X 7-ml tumor-1, about 5-10 times lower than all previous
estimates obtained in vitro and in vivo. To resolve this dilemma we used
doubly labeled [1-14C; 9,10-3H]palmitate and found that under aerobic
conditions, in vitro, EAT formed 3H2O and 14CO2 at nearly equal rates.
These rates were suppressed markedly but unequally at low PO2. Anaerobic
suppression of 14CO2 formation greatly exceeded that of 3H2O formation. As
a result 3H2O/14CO2 reached a value of congruent to 10 at low PO2. Our data
indicate that under the nearly anaerobic conditions of a growing EAT in
vivo, the partial beta-oxidation of FA to 2C + H2O takes place at a 5 to 10
times faster rate than the complete oxidation of FA to CO2 + H2O. This
finding can account for earlier apparent inconsistencies in the literature,
since aerobic studies of 14C-FA oxidation to 14CO2 in vitro and of 3H-FA
oxidation to 3H2O under nearly anaerobic conditions would both overestimate
greatly the rate of FA oxidation to CO2 by EAT in vivo.
