Tissue-specific mutational spectra of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline in the liver and bone marrow of lacI transgenic mice.
2-Amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) is a food-borne heterocyclic amine, so clarification of its mutational spectrum is important for evaluation of its carcinogenic risk to humans. The mutational spectrum of MeIQ was investigated in the liver and bone marrow of transgenic mice carrying the lacI gene. By PCR--single-strand conformation polymorphism analysis and sequencing of the lacI gene, 81 and 61 mutations were identified in 80 and 59 mutants obtained from the liver and bone marrow respectively of three transgenic mice given food containing 300 p.p.m. MeIQ. In the liver, G-->T transversions were the most frequent, accounting for 46% of the total mutations, followed by G-->A transitions (25%). In the bone marrow, four types of mutations, G-->T transversions, G-->A transitions, complex mutations and one base deletions, each accounted for 21-23% of the total mutations. Of the total mutations, 10% were found at nucleotide 92 in the liver and at nucleotide 222 in the bone marrow. Analysis of 27 and 13 mutants from the liver and bone marrow respectively of control mice showed frequent G-->A transitions at CpG sites. These findings suggest a tissue-specific mechanism of mutagenesis.
Ushijima
T
T
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Hosoya
Y
Y
Ochiai
M
M
Kushida
H
H
Wakabayashi
K
K
Suzuki
T
T
Hayashi
M
M
Sofuni
T
T
Sugimura
T
T
Nagao
M
M
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism*; D018736:DNA Adducts; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009152:Mutagenicity Tests; D009928:Organ Specificity; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011804:Quinolines / Q000493:pharmacokinetics / Q000633:toxicity*; D011994:Recombinant Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*
D001426:Bacterial Proteins; D018736:DNA Adducts; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D011804:Quinolines; D011994:Recombinant Proteins; D012097:Repressor Proteins; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline