MODIFICATION OF THE EXPRESSION OF ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE-INDUCED DIFFERENTIATED FUNCTIONS IN NEUROBLASTOMA-CELLS BY BETA-CAROTENE AND D-ALPHA-TOCOPHERYL SUCCINATE

Objective: The role of beta-carotene and vitamin E in modifying the ef fect of cell differentiating agent has not been studied. This study ha s investigated the effects of beta-carotene and d-alpha-tocopheryl suc cinate (alpha-TS) on adenosine 3',5'-cyclic monophosphate (cAMP) induc ed differentiated functions in murine neuroblastoma cells (NBP2) in cu lture. Methods: Prostaglandin E(1) (PGE(1)), a stimulator of adenylate cyclase, and 4(-3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-172 4), an inhibitor of cyclic nucleotide phosphodiesterase. were used to induce differentiation in NB cells. Results: Both beta-carotene and al pha-TS markedly enhanced the level of morphologic differentiation (neu rite formation) induced by both PGE, and R020-1724. However, beta-caro tene and alpha-TS by themselves were ineffective. These vitamins incre ased tyrosine hydroxylase (TH) activity. However, beta-carotene did no t significantly affect PGE(1) and R020-1724-stimulated rise in Tn acti vity. alpha-TS at a higher concentration inhibited PGE(1)- and R020- 1 724-stimulated increase in TH activity. None of the above treatments a ffected basal choline acetyltransferase (ChAT) activity. beta-carotene and alpha-TS caused a transient increase in cAMP level, and they also enhanced the effect of PGE(1) and R020-1724 on cAMP level in a transi ent manner. Conclusion: These results suggest that a-carotene and LU-T S modify the effects of cAMP stimulating agents on differentiation of NB cells in culture.