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.