Induction of gene amplification by 5-aza-2'-deoxycytidine.
Treatment of Syrian hamster kidney cells with the demethylating agent 5-aza-2'-deoxycytidine (azadC) increased both the frequency and the rate of gene amplification appreciably. AzadC caused substantial DNA demethylation, which is likely to be responsible. The magnitude of the increases depended on the concentrations of both azadC and the drug used for selection. A transient stress response is not responsible since the increases were not dependent on cytotoxicity and were still apparent after several weeks. We discuss mechanisms by which azadC treatment may induce amplification by rendering DNA more prone to this process or by increasing the transcription of genes whose protein products stimulate amplification.
Perry
M E
ME
Department of Molecular Biology, Imperial Cancer Research Fund, Lincoln's Inn Fields, London, Great Britain.
Rolfe
M
M
McIntyre
P
P
Commane
M
M
Stark
G R
GR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015139:Blotting, Southern; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics; D005784:Gene Amplification / Q000187:drug effects*; D008647:Mesocricetus; D008745:Methylation; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D000970:Antineoplastic Agents; D001224:Aspartic Acid; D000077209:Decitabine; C013195:sparfosic acid; D004247:DNA; D001374:Azacitidine; D010746:Phosphonoacetic Acid