Specificity in the methylation of DNA by N-nitroso compounds.
A sequencing assay was used to determine the reactivity of N-nitroso compounds that are simple methylating agents with individual nucleotides in a defined DNA sequence. The maximal difference in reactivity between guanines is about five fold. DNA in the Z, cruciform and H conformations was shown to be methylated by N-methyl-N-nitrosourea in a manner which was indistinguishable from the reactivity of B-DNA. Electronic factors rather than steric factors appear to dominate the methylation reaction. Transcriptionally active genes were shown to be methylated by N-nitroso compounds in vivo more extensively than untranscribed genes. The results suggest that local sequence, secondary conformation and transcriptional activity may all influence the carcinogenic potential of N-nitroso compounds.
Milligan
J R
JR
Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute, Canada.
Skotnicki
S
S
Lu
S J
SJ
Archer
M C
MC
D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D011905:Genes, ras; D008745:Methylation; D009603:Nitroso Compounds / Q000378:metabolism / Q000633:toxicity*; D009690:Nucleic Acid Conformation
D009603:Nitroso Compounds; D004247:DNA