Induction of DNA polymerase alpha and terminal deoxynucleotidyl transferase in the human lymphoblastoid cell line Molt-4 by the immunomodulator bestatin.

The influence of the immunomodulator bestatin on the expression of terminal deoxynucleotidyl transferase and of DNA polymerase alpha and beta in Molt-4 cells has been studied. Bestatin was found to stimulate cell growth within the range of 0.3-33 microM, while concentrations higher than 300 microM were inhibitory during an incubation period of 48 h. The cell surface bound microsomal leucine aminopeptidase (bestatin receptor) activity decreased gradually during incubation at concentrations of bestatin above 3 microM. This effect was also observed after incubation with amastatin, but not with leupeptin or tunicamycin. Determinations of the activities of DNA synthesizing enzymes from bestatin-treated Molt-4 cells revealed a direct correlation between the decrease of the surface bound microsomal leucine aminopeptidase activity and the increase of the terminal deoxynucleotidyl transferase and DNA polymerase alpha activity; the DNA polymerase beta activity remained unchanged. From these experiments it is hypothesized that bestatin might cause a promoting effect on the differentiation processes of precursor T cells in vivo.