Mutational specificities of environmental carcinogens in the lac1 gene of Escherichia coli, VII: The host-mediated assay and its comparison with in vitro mutagenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.
To investigate the influence of different types of metabolic activation (9,000 x g supernatant (S9) activation vs. a host-mediated approach) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced mutational specificity, we determined by DNA sequencing the distribution of forward mutations recovered in the N-terminal region of the lac1 gene of Escherichia coli. After activation with the S9 liver fraction from rats treated with Aroclor 1254, a diverse spectrum of mutations was recovered, with 55% of the events being G:C-->A:T transitions. In contrast, after the host-mediated assay in mice, G:C-->A:T transitions accounted for over 94% of the mutations recovered. Generally, NNK metabolism can proceed through two distinct pathways, involving either alpha-methyl or methylene hydroxylation. These two pathways produce different distributions of DNA damage. The difference in the mutational spectra we observed thus likely reflects the difference in the contributions of each pathway under the two different treatment conditions.
Jiao
J
J
Department of Biology, University of Victoria, British Columbia, Canada.
Guttenplan
J B
JB
Glickman
B W
BW
Anderson
M W
MW
Xin
L Y
LY
Zielenska
M
M
D001483:Base Sequence; D001711:Biotransformation; D002273:Carcinogens / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics*; D007785:Lactose / Q000235:genetics*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009602:Nitrosamines / Q000494:pharmacology*
D002273:Carcinogens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D007785:Lactose