Effect of p-aminobenzoic acid N-xyloside sodium salt (K-247) on metabolism and functions of normal lymphocytes and leukemic cells.
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.
D010129:4-Aminobenzoic Acid / Q000494:pharmacology*; D062365:Aminobenzoates / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010587:Phagocytosis / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology; D062366:para-Aminobenzoates
D062365:Aminobenzoates; D000970:Antineoplastic Agents; D010743:Phospholipids; D062366:para-Aminobenzoates; C035660:4-aminobenzoic acid-N-xyloside; D002118:Calcium; D010129:4-Aminobenzoic Acid