Methylation of DNA by three N-nitroso compounds: evidence for sequence specific methylation by a common intermediate.
Methylation in vitro of calf thymus DNA, a supercoiled plasmid, poly(dG).poly(dC), and poly(dGdC).poly(dGdC) by N-nitroso(acetoxy-methyl)methylamine and N-nitroso(acetoxybenzyl)methylamine in the presence of esterase, and by N-nitrosomethylurea was investigated. Although there were differences in the amounts of 7-methylguanine and O6-methylguanine formed in the various DNA substrates, the methylation pattern was the same for each of these methylating agents. The three compounds reacted identically when methylation of a portion of a 345 bp restriction fragment of the plasmid pBR322 was examined at nucleotide resolution by a sequencing assay. They also showed a tendency to react preferentially with particular guanines. These data suggest that the three N-nitroso compounds methylate DNA via a common intermediate such as the methyl diazonium ion, which exhibits some sequence specificity.
Milligan
J R
JR
Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Hirani-Hojatti
S
S
Catz-Biro
L
L
Archer
M C
MC
D001483:Base Sequence; D004247:DNA; D004262:DNA Restriction Enzymes; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives; D006147:Guanine / Q000031:analogs & derivatives; D008745:Methylation; D008770:Methylnitrosourea; D009602:Nitrosamines / Q000378:metabolism; D009603:Nitroso Compounds; D010957:Plasmids; D011089:Polydeoxyribonucleotides
D009602:Nitrosamines; D009603:Nitroso Compounds; D011089:Polydeoxyribonucleotides; C019530:poly(dC-dG); C061845:N-nitroso(acetoxybenzyl)methylamine; C014659:methyl(acetoxymethyl)nitrosamine; D006147:Guanine; C008450:7-methylguanine; D008770:Methylnitrosourea; D004247:DNA; C008449:O-(6)-methylguanine; D004262:DNA Restriction Enzymes; D004128:Dimethylnitrosamine