Characterization of acetate metabolism in tumor cells in relation to cell proliferation: Acetate metabolism in tumor cells

To reveal the metabolic fate of acetate in neoplasms that may characterize the accumulation patterns of [1-C-11] acetate in tumors depicted by positro n emission tomography. Four tumor cell lines (LS174T, RPMI2650, A2780, and A375) and fibroblasts in growing and resting states were used. In uptake ex periments, cells were incubated with[1-C-14]acetate for 40 min. [C-14]CO2 w as measured in the tight-air chamber, and the metabolites in cells were ide ntified by thin layer chromatography and paper chromatography. The glucose metabolic rate of each cell line was measured with [2,6-H-3]2-deoxy-glucose (DG), and the growth activity of each cell line was estimated by measuring the incorporation of [H-3]methyl thymidine into DNA. Compared with resting fibroblasts, all four tumor cell lines showed higher accumulation of 14C a ctivity from [1-C-14]acetate. These tumor-to-normal ratios of [1-C-14]aceta te were larger than those of DG. Tumor cells incorporated C-14 activity int o the lipid-soluble fraction, mostly of phosphatidylcholine and neutral lip ids, more prominently than did fibroblasts. The lipid-soluble fraction of C -14 accumulation in cells showed a positive correlation with growth activit y, whereas the water-soluble and CO2 fractions did not. These findings sugg est that the high tumor-to-normal ratio of [1-C-14]acetate is mainly due to the enhanced lipid synthesis, which reflects the high growth activity of n eoplasms. This in vitro study suggests that [1-C-11]acetate is appropriate for estimating the growth activity of tumor cells. (C) 2001 Elsevier Scienc e Inc. All rights reserved.