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

• Published in: Mutation research Vol. 452; no. 1; p. 101
• Main Authors: Stuart, G R, Thorleifson, E, Okochi, E, de Boer, J G, Ushijima, T, Nagao, M, Glickman, B W
• Format: Journal Article
• Language: English
• Published: Netherlands 20.07.2000
• Subjects: Animals; Animals, Genetically Modified; Bacterial Proteins - genetics; Base Sequence; Carcinogens - toxicity; Colon - drug effects; Colon - metabolism; DNA - chemistry; DNA - drug effects; DNA - genetics; DNA Mutational Analysis; Escherichia coli Proteins; Female; Frameshift Mutation; Imidazoles - toxicity; Lac Repressors; Male; Mice; Mutagenesis, Insertional; Mutation; Point Mutation; Rats; Rats, Inbred F344; Repressor Proteins - genetics; Sequence Deletion; Transcription Factors - genetics; Transgenes - drug effects; Transgenes - genetics; Viral Proteins
• ISSN: 0027-5107
• DOI: 10.1016/S0027-5107(00)00058-0

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.