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)-methyldeoxyadenosine (MDA). The possible biological effect of this nucleoside on eukaryotic cells has been studied on different tumor cell lines. Addition of MDA to C6.9 glioma cells triggers a differentiation process and the expression of the oligodendroglial marker 2',3'-cyclic nucleotide 3'phosphorylase (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 cell differentiation remains unclear, but is related to cell cycle modifications. These data point out the potential interest of N(6)-methyldeoxyadenosine as a novel antitumoral and differentiation agent. They also raise the intriguing question of the loss of adenine methylation in mammalian DNA. Furthermore, the finding that a methylated nucleoside found in bacterial DNA induces a biological process might have implications in gene therapy approaches when plasmid DNAs are injected into humans.
Ratel
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D
INSERM U318, CHU Michallon, 38033 Grenoble cedex 9, France.
Boisseau
S
S
Davidson
S M
SM
Ballester
B
B
Mathieu
J
J
Morange
M
M
Adamski
D
D
Berger
F
F
Benabid
A L
AL
Wion
D
D
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000096:biosynthesis; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D003839:Deoxyadenosines / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D009124:Muscle Proteins; D018302:Neoplasms, Neuroepithelial / Q000378:metabolism*; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases; D051381:Rats; D018243:Teratocarcinoma / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D008840:Microfilament Proteins; D009124:Muscle Proteins; C432366:N(6)-methyldeoxyadenosine; C058992:Tagln protein, mouse; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571337:CNP protein, human; C571338:Cnp protein, mouse; C571339:Cnp protein, rat