POLYAMINE BIOSYNTHESIS ENZYMES IN THE INDUCTION AND INHIBITION OF DIFFERENTIATION IN FRIEND-ERYTHROLEUKEMIA CELLS

Abstract

L-Ornithine decarboxylase (ODC) activity in cultures of Friend erythroleukemia cells induced to differentiate with various compounds [mouse] was examined. Based on ability to stimulate ODC activity, the inducers tested could be divided into 2 categories. Inducers of the 1st class, among which were dimethyl sulfoxide and hexamethylene bisacetamide, stimulated ODC activity and were inhibited by dexamethasone and the phorbol diester, 12-O-tetradecanoylphorbol-13-acetate. Specific inhibitors of polyamine biosynthesis, such as methylglyoxal bis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, and the ornithine analogs, .alpha.-methylornithine and .alpha.-hydrazinoornithine, inhibited the induction of Friend erythroleukemia cell differentiation. The inhibition of induced differentiation by this class of compounds could be abrogated by spermine, spermidine or putrescine. Inducers of the 2nd class, among which were sodium butyrate, actinomycin D and aminonucleoside of puromycin, had little or no stimulatory effect on ODC and were inhibited only by bromodeoxyuridine. The effect of bromodeoxyuridine, which inhibits inducers of both classes, was not abrogated by polyamines.