The complexity of nitrosoguanidine mutagenesis increases with size: observations of the mutational specificity of N-propyl-N'-nitro-N-nitrosoguanidine.
The mutational specificity of the monofunctional alkylating agent N-propyl-N'-nitro-N-nitrosoguanidine (PNNG) has been determined through the DNA sequence characterization of 109 LacI- mutations of Escherichia coli. The predominant mutation induced was the G:C----A:T transition (73%), presumably the result of O6-propylguanine damage. Transversions constituted 18% of the mutants, almost entirely due to G:C----T:A (9%) and A:T----C:G (8%) events. Two identical deletions, one single base pair frameshift and a tandem double base change were also recovered. In contrast, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was previously found to induce only transitions, again predominantly G:C----A:T events (98%). Moreover, the site specificity observed for PNNG-induced G:C----A:T transitions is quite distinct from that induced by MNNG. G:C----A:T transitions recovered following PNNG treatment do not appear to be influenced by neighbouring base sequence to the extent seen for MNNG.
van der Vliet
G M
GM
Biology Department, York University, Toronto, Ontario, Canada.
Zielenska
M
M
Anderson
M W
MW
Glickman
B W
BW
D001482:Base Composition; D001483:Base Sequence; D004261:DNA Replication / Q000187:drug effects; D004269:DNA, Bacterial / Q000187:drug effects / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D005796:Genes / Q000187:drug effects; D005798:Genes, Bacterial / Q000187:drug effects*; D008769:Methylnitronitrosoguanidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008969:Molecular Sequence Data; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation
D004269:DNA, Bacterial; D009153:Mutagens; D008769:Methylnitronitrosoguanidine; C013659:propyl-N'-nitro-N-nitrosoguanidine