Effect of p-aminobenzoic acid N-xyloside sodium salt (K-247) on metabolism and functions of normal lymphocytes and leukemic cells.

Abstract

An N-xyloside derivative of p-aminobenzoic acid, K-247, was investigated for the ability to induce changes of Phospholipid metabolism and membrane transport in murine splenic lymphocytes and leukemic cells. K-247 induced an increase of [3H] methyl group incorporation into phospholipid in both normal lymphocytes and leukemic cells (L-1210 and M1 cells). However, K-247 accelerated the turnover of phosphatidylinositol (PI) measured by [32P] incorporation into PI in L-1210 cells and Ml cells but not in normal lymphocytes. 45Ca2+ influx into normal lymphocytes and leukemic cells was also increased by K-247. A methyltransferase inhibitor, 5'-deoxy-5'-S-isobutyl adenosine (SIBA), suppressed both the increase of phospholipid methylation and that of Ca2+ influx. It seemed that Ca2+ transport might be regulated by membrane phospholipid methylation. On the other hand, K-247 was found to suppress [3H] aminoisobutylic acid (AIB) uptake into L-1210 cells and Ml cells. Protein synthesis in L-1210 cells and Ml cells slightly decreased but RNA and DNA syntheses in both normal and leukemic cells were not affected by K-247. These results suggest that K-247 mainly acts on cell membranes, which are more sensitive to K-247 in leukemic cells than in normal lymphocytes. K-247 also induced differentiation of Ml cells into macrophages and granulocytes with phagocytic activity and morphological characteristics. Moreover, K-247 elevated the Con A response of murine thymocytes, most of which were immature T cells and had low reactivity to Con A, and caused a decrease of Thy 1.2 antigen on thymocytes. It seemed that K-247 also affected maturation of thymocytes.