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In vivo mutagenesis induced by benzo[ a ]pyrene instilled into the lung of gpt delta transgenic mice
Author(s) -
Hashimoto Akiko H.,
Amanuma Kimiko,
Hiyoshi Kyoko,
Takano Hirohisa,
Masumura Kenichi,
Nohmi Takehiko,
Aoki Yasunobu
Publication year - 2005
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20098
Subject(s) - transversion , mutagenesis , benzo(a)pyrene , mutagen , microbiology and biotechnology , mutation frequency , guanine , mutant , in vivo , mutation , biology , pyrene , genetically modified mouse , ratón , transgene , chemistry , carcinogen , nucleotide , gene , genetics , immunology , astrobiology
Benzo[ a ]pyrene (B[ a ]P) is a ubiquitous airborne pollutant whose mutagenicity has been evaluated previously by oral and intraperitoneal administration to experimental animals. In this study, mutagenesis in the lungs, the target organ of air pollutants, was examined after a single intratracheal instillation of 0–2 mg B[ a ]P into gpt delta transgenic mice. Intratracheal injection of B[ a ]P resulted in a statistically significant and dose‐dependent increase in gpt mutant frequency as measured by 6‐thioguanine selection. The mutant frequencies at B[ a ]P doses of 0.5, 1, and 2 mg were 2.8, 4.2, and 6.8 times higher than the frequency seen in nontreated mice (0.60 ± 0.13 × 10 −5 ). The most frequent mutations induced by B[ a ]P treatment were G:C→T:A transversions, which are characteristic of B[ a ]P mutagenesis in other models, and single‐base deletions of G:C base pairs. To characterize the hotspots of B[ a ]P‐induced mutations in the gpt gene, we analyzed sequences adjacent to the mutated G:C base pairs. Guanine bases centered in the nucleotide sequences C G T, C G A, and C G G were the most frequent targets of B[ a ]P. Our results indicate that intratracheal instillation of B[ a ]P into gpt delta mice causes a dose‐dependent increase in gpt mutant frequency in the lung, and that the predominant mutation induced is G:C→T:A transversion. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.