Differential stimulation of lymphocyte cell growth in vitro by cephalosporins

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Abstract
The in vitro effect of three cephalosporins (cefodizime, cefotaxime, and ceftizoxime) on the growth of the following lymphocytes or their derivatives was tested: L 5178y mouse lymphoma cells, Molt-4 cells, and murine splenic lymphocytes. Within the concentration range of 0.1 to 50 microM, the cephalosporins had no effect on L 5178y cell growth. However, Molt-4 cell growth was significantly stimulated by 0.3 to 20 microM cefotaxime and cefodizime but was not influenced by ceftizoxime. Binding studies with [14C]cefotaxime revealed that the Molt-4 cells responding to the drug bind this cephalosporin to their cell surface (1.9 X 10(5) molecules per cell); no significant binding was observed in the assays with L 5178y cells. Determinations of the extractable activities of DNA-synthesizing enzymes from cefodizime-treated Molt-4 cells showed a direct correlation between cell growth and DNA polymerase alpha as well as terminal deoxynucleotidyl transferase activity; the DNA polymerase beta activity remained unchanged. Cefodizime (0.15 to 50 microM) which was added to mouse spleen cell cultures significantly increased [3H]thymidine incorporation into lymphocytes. This stimulatory effect was less pronounced in concanavalin A-stimulated cultures. These findings suggest that some cephalosporins display a growth-stimulating influence on some lymphocyte populations.