title: Interpretation of mutational spectra from different genes: analyses of PhIP-induced mutational specificity in the lacI and cII transgenes from colon of Big Blue rats.
abstract: The cII assay provides an alternative choice to the lacI transgene for mutational studies involving Big Blue(R) transgenic mice and rats, or permits the evaluation of mutational responses in both genes. Here, we compare the mutational response of the cII gene from colon of Big Blue(R) F344 rats treated with a dietary mutagen and animal carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), to those previously determined in the lacI transgene from colon of the same group of animals. A cursory inspection of PhIP-induced mutational spectra (MS) in cII and lacI suggests that the two transgenes respond differently to PhIP-induced mutation. However, a more thorough analysis of the MS in the two transgenes, including consideration of the number of mutational target sequences in each gene and nearest neighbor analyses of mutated nucleotides, indicates that PhIP-induced mutational specificity is similar in both genes. The evaluation of PhIP-induced mutational responses in these two transgenes serves as a model for intergenic mutational analyses.
authors.affiliation: Centre for Environmental Health and the Department of Biology, University of Victoria, Canada. gstuart@uvic.ca
authors.forename: G R
authors.initials: GR
authors.lastname: Stuart
authors.forename: E
authors.initials: E
authors.lastname: Thorleifson
authors.forename: E
authors.initials: E
authors.lastname: Okochi
authors.forename: J G
authors.initials: JG
authors.lastname: de Boer
authors.forename: T
authors.initials: T
authors.lastname: Ushijima
authors.forename: M
authors.initials: M
authors.lastname: Nagao
authors.forename: B W
authors.initials: BW
authors.lastname: Glickman
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D004252:DNA Mutational Analysis; D029968:Escherichia coli Proteins; D005260:Female; D016368:Frameshift Mutation; D007093:Imidazoles / Q000633:toxicity; D056968:Lac Repressors; D008297:Male; D051379:Mice; D016254:Mutagenesis, Insertional; D009154:Mutation; D017354:Point Mutation; D051381:Rats; D011916:Rats, Inbred F344; D012097:Repressor Proteins / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics; D019076:Transgenes / Q000187:drug effects / Q000235:genetics*; D014764:Viral Proteins
chemical_list: D001426:Bacterial Proteins; D002273:Carcinogens; D029968:Escherichia coli Proteins; D007093:Imidazoles; D056968:Lac Repressors; D012097:Repressor Proteins; D014157:Transcription Factors; D014764:Viral Proteins; C039000:cII protein, bacteriophage lambda; D004247:DNA; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine