Differential stimulation of lymphocyte cell growth in vitro by cephalosporins

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.