Mutational specificity of N-nitrosodimethylamine: comparison between in vivo and in vitro assays.
We have determined the DNA alterations recovered after treatment with Aroclor 1254-treated rat S9-activated N-nitrosodimethylamine (NDMA) in the N-terminal region of the lacI gene of E. coli. A total of 125 independent LacI-d mutants of E. coli were characterized by DNA sequencing. Consistent with the known methylating ability of this compound, the predominant mutation was the G:C-->A:T transition, which accounted for 90% of all the mutations recovered. Non G:C-->A:T events include 2 G:C-->T:A, 2 G:C-->C:G, 2 A:T-->G:C, 3 A:T-->T:A and 3 frameshifts. Contingency analysis reveals that NDMA-induced mutations recovered after in vitro activation (S9) have a spectrum very similar to that previously obtained after in vivo activation employing a mouse host-mediated assay. In both systems, G:C-->A:T events clearly dominate and their distribution reveals similar site-specificity. Moreover, the proportion and kind of non-G:C-->A:T events are also similar.
Jiao
J
J
Department of Biology, York University, Toronto, Ont., Canada.
Glickman
B W
BW
Anderson
M W
MW
Zielinska
M
M
D000818:Animals; D001483:Base Sequence; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000032:analysis; D004789:Enzyme Activation; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D016368:Frameshift Mutation; D007763:Lac Operon / Q000187:drug effects*; D008099:Liver / Q000201:enzymology; D008110:Liver Extracts; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D009603:Nitroso Compounds / Q000378:metabolism / Q000633:toxicity*; D017354:Point Mutation
D004269:DNA, Bacterial; D008110:Liver Extracts; D009153:Mutagens; D009603:Nitroso Compounds; C008651:4-nitrosodimethylaniline; D003577:Cytochrome P-450 Enzyme System