[H-3] INOSITOL HEXAPHOSPHATE (PHYTIC ACID) IS RAPIDLY ABSORBED AND METABOLIZED BY MURINE AND HUMAN-MALIGNANT CELLS IN-VITRO

To test the hypothesis that the antineoplastic activity of phytic acid [inositol hexaphosphate (InsP(6))] is a result of rapid intake by the cells and its conversion to lower inositol phosphates (InsP(1-5)), th ereby affecting the intracellular inositol phosphate pool, YAC-1 (mous e T cell leukemia), K562 (human erythroleukemia) and HT-29 (human colo n adenocarcinoma) cell lines were incubated at 37 degrees C with [H-3] InsP(6). After 1 h, 31.3 +/- 3.1% of administered radioactivity was ta ken up by YAC-1 cells, 6.2 +/- 0.9% by K562 cells and 6.6 +/- 3.8% by HT-29 cells. Differential centrifugation and high resolution subcellul ar fractionation of cell homogenates demonstrated that within the vari ous cellular compartments, 80% (HT-29) to 97% (YAC-1) of the total rad ioactivity was in the cytosol. Kinetic study showed that the peak of t he total absorption was obtained after 30 min of cell exposure to radi olabeled InsP(6), after with a plateau was reached. Analysis of the ra dioactivity accumulated within the cells showed variable proportions o f myo-inositol and InsP(1-6), with a preponderance of InsP(1) and InsP (2). The presence of [H-3]myo-inositol and [3H]InsP(1-6) suggests that InsP(6) may, in some cells at least, be absorbed as such and that a v ariable degree of dephosphorylation of InsP(6) takes place both extra- and intracellularly.