The bacterial nucleoside N-6-methyldeoxyadenosine induces the differentiation of mammalian tumor cells

Contrary to bacterial DNA, mammalian DNA contains very little if any N-6-me thyldeoxyadenosine (MDA). The possible biological effect of this nucleoside on eukaryotic cells has been studied on different tumor cell lines. Additi on of MDA to C6.9 glioma cells triggers a differentiation process and the e xpression of the oligodendroglial marker 2 ' ,3 ' -cyclic nucleotide 3 ' ph osphorylase (CNP). The biological effects of N-6-methyldeoxyadenosine were not restricted to C6.9 glioma cells since differentiation was also observed on pheochromocytoma and teratocarcinoma cell lines and on dysembryoplastic neuroepithelial tumor cells. The precise mechanism by which MDA induces ce ll differentiation remains unclear, but is related to cell cycle modificati ons. These data point out the potential interest of N-6-methyldeoxyadenosin e as a novel antitumoral and differentiation agent. They also raise the int riguing question of the loss of adenine methylation in mammalian DNA. Furth ermore, the finding that a methylated nucleoside found in bacterial DNA ind uces a biological process might have implications in gene therapy approache s when plasmid DNAs are injected intoliumans. (C) 2001 Academic Press.