Fatty Acid Oxidation to H2O by Ehrlich Ascites Carcinoma in Mice1

aerobic conditions, it is imperative that such observations be verified and extended in the living animal. To our knowledge, there has been no report of any direct measurement of tumor FFA oxidation in vivo. The only indirect estimate of FFA oxidation by Ehrlich ascites carci noma in vivo is that reported by Mermier and Baker (22) using [9,10-3H]palmitate complexed to serum albumin. Ac cording to these authors' calculations, the rate of FFA oxidation by the tumor cells (220 nmol FFA per mm per 7 ml tumor) was approximately 20 times greater than the FA requirement for net growth. Such a high oxidation rate is surprising not only because cancer cells tend to have somewhat lower oxidative rates than do noncancerous tissues in vitro (35) but also because, as mentioned, the oxygen supply available to a large ascites tumor growing in the peritoneal cavity is apparently sparse. In fact, Mermier and Baker did not carry out any direct measurements of oxidation products. Instead, they assumed that, after the injection of [9,i0-3H]palmitate into the tumor, any radioac tivity that could not be accounted for in tumor lipids and host tissues must have been lost due to FFA oxidation by the cancer cells. In the present study, we have measured the FFA oxidation rate by Ehmlich ascites carcinoma in vivo using the appear ance of 3H20, one of the direct products of [3H]FFA oxida tion. To avoid the possible overestimation of the oxidation rate, we have taken into account the possible formation of 3H2Oby desaturation of [9,10-3H]palmitate to monounsatu rated FA. Our analysis was based upon the kinetics of labeled water formation and transport after i.p. injection of [9,10-3H]palmitate and 3H20 as well as the formation of palmitoleate (16:1)@ and cis-vaccenate (18:1) from [1“C]palmitateby the tumor in vivo. Using the new data in conjunction with the previously developed tumor FA turn over model (22), we have again calculated that the Ehmlich ascites carcinoma oxidizes FFA at a very rapid rate (approx imately 60 nmol FFA per mm per 7-mI tumor) despite the apparent deficiency of oxygen in the peritoneal cavity. Although this newly calculated rate is lower than the earlier indirect estimate (22), the FFA oxidation rate still appears to be 6 times more rapid than the net rate of FFA utilization for tumor growth in the 10-day-old Ehmlichascites carci noma.