Mutational specificity of N-nitrosodimethylamine: comparison between in vivo and in vitro assays
Jiao, J.; Glickman, B.W.; Anderson, M.W.; Zielinska, M.
Mutation Research 301(1): 27-31
1993
ISSN/ISBN: 0027-5107 PMID: 7677940 Document Number: 415574
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 Escherichia 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 fwdarw A:T transition, which accounted for 90% of all the mutations recovered. Non G:C fwdarw A : T events include 2 G:C fwdarw T:A, 2 G:C fwdarw C:G, 2 A:T fwdarw G:C, 3 A:T fwdarw 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 vitro activation (S9) have a spectrum very similar to that previously obtained after in vivo activation employing a mouse host-mediated assay. In both system, G:C fwdarw A:T events clearly dominate and their distribution reveals similar site-specificity. Moreover, the proportion and kind of non-G:C fwdarw A:T events are also similar.