INDUCTION OF SPERMIDINE SPERMINE N(1)-ACETYLTRANSFERASE IN HUMAN BREAST-CARCINOMA CELLS - A POSSIBLE ROLE FOR CALCIUM

Methylglyoxal bis(guanylhydrazone) (MGBG) a structural analogue of spe rmidine produced a dose-dependent induction of cytosolic spermidine/sp ermine N1-acetyltransferase (N1-SAT) in the human breast carcinoma cel l line, T47-D. Intracellular accumulation of MGBG was found to be satu rable and the drug produced characteristic effects on intracellular po lyamines, decreasing spermidine and spermine content, with concomitant increases in putrescine levels. The MGBG-induced increase in N1-SAT a ctivity was potentiated by both tetronasin, a calcium ionophore, and f elodipine, a calcium channel blocking agent. Only tetronasin was an ac tive inducer of the enzyme when used alone. Both drugs influenced intr acellular MGBG content but in opposite directions: tetronasin increase d MGBG content while felodipine decreased it. Therefore, the potentiat ion of N1-SAT induction is not simply the result of increased intracel lular accumulation of MGBG but is more likely to be related to the con centration of intracellular free calcium in these cells.