1-Methylnicotinamide stimulates cell growth, causes DNA hypermethylation and inhibits induced differentiation of Friend erythroleukemia cells.

Abstract

Formation of 1-methylnicotinamide (1-MN) occurs via enzymatic methylation of excess nicotinamide (NA) by nicotinamide methyltransferase, a phase II detoxification enzyme which is found predominantly in the liver and kidney (1,2). Although 1-MN is known to be the primary metabolite of excess NA, the cellular functions of this compound are not well understood. 1-MN was found to stimulate DNA synthesis and cell growth of cultured hepatocytes (2). We have previously noted (3) that 1-MN has an unique effect of causing DNA hypermethylation in Friend erythroleukemia cells (FELCs). Induced erythroid differentiation of FELCs, as determined by increased hemoglobin expression, has been correlated with a transient genome-wide DNA hypomethylation using a variety of chemical inducers including NA (4-9). However, direct evidence for a causal involvement of DNA hypomethylation in the process of FELC differentiation is lacking. In this study, 1-MN was combined in FELC culture with several chemical inducers which are known to cause DNA hypomethylation, in an effort to reverse the induction of differentiation by antagonism of the DNA hypomethylation.