Aberrant de novo methylation of DNA after treatment of murine cells with N-acetoxy-N-2-acetylaminofluorene.
The ultimate chemical carcinogen N-acetoxy-N-2-acetylaminofluorene inhibits the enzymatic methylation of newly replicated DNA in cultured mouse P815 cells in a dose-dependent manner. After removal of the carcinogen, a significant de novo methylation of newly replicated DNA takes place, the level of methylation being higher than in control cultures. This aberrant methylation persists in the absence of N-acetoxy-N-2-acetylaminofluorene in subsequent cell cycles. Cellular cloning experiments suggest that N-acetoxy-N-2-acetylaminofluorene treatment leads to two distinct sets of cells, one with a higher and another with a lower extent of enzymatic methylation of DNA, contrasting to the apparent uniform methylation pattern in control clones.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000099:Acetoxyacetylaminofluorene / Q000633:toxicity*; D000818:Animals; D001482:Base Composition; D002460:Cell Line; D002999:Clone Cells; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics* / Q000302:isolation & purification; D007700:Kinetics; D008745:Methylation; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D010954:Plasmacytoma / Q000378:metabolism*
D004273:DNA, Neoplasm; D000099:Acetoxyacetylaminofluorene; D015073:2-Acetylaminofluorene