Treatment with phorbol esters leads to spermine depletion and inhibition of DNA synthesis in phytohemagglutinin-activated bovine lymphocytes.

Phorbol 12-myristate-13-acetate (PMA) inhibited an increase in [3H]thymidine incorporation induced by phytohemagglutinin (PHA) in cultured bovine lymphocytes. Cellular levels of putrescine increased in the presence of PHA and PMA but the levels of spermidine and spermine had decreased to the control levels by 40 h. In cells treated with PHA and PMA, the activity of spermidine/spermine N1-acetyltransferase, a rate-limiting enzyme in polyamine biodegradation, was stimulated synergistically. Phorbol esters with tumor-promoting ability also stimulated the enzyme activity and a reciprocal correlation between the enzyme activity and DNA synthesis was observed. Addition of spermine reversed the PHA- and PMA-induced inhibition of DNA synthesis but putrescine and spermidine failed to restore it. These results suggest that the enhancement of spermidine/spermine N1-acetyltransferase activity results in the depletion of intracellular spermine and a concomitant decrease in DNA synthesis.