ArticleGenes and environment : the official journal of the Japanese Environmental Mutagen Society2015
Alterations in the mutagenicity and mutation spectrum induced by benzo[a]pyrene instilled in the lungs of gpt delta mice of various ages.
Article in Genes and environment : the official journal of the Japanese Environmental Mutagen Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 5 citations in OpenAlex.
- The 28 + 28 day design is an effective sampling time for analyzing mutant frequencies in rapidly proliferating tissues of MutaMouse animals.Archives of toxicology · 2021Article
- Change over time of the mutagenicity in the lungs ofGenes and environment : the official journal of the Japanese Environmental Mutagen Society · 2018Article
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7 authors at 3 institutions in 1 country.
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Abstract
introductionTo examine whether the mutagenic potential of lung exposure to air-borne environmental mutagens is age dependent, we administered 1 mg of benzo[a]pyrene intratracheally to 11- and 24-month old (middle-aged and old, respectively) gpt delta transgenic mice that harbor gpt (guanine phosphoribosyltransferase) genes integrated in the genomic DNA as a target for mutation detection, and then analyzed the benzo[a]pyrene-induced and spontaneous in vivo mutations and mutation spectrum in the lungs.
resultsThe mutant frequencies in the lungs of the 11- and 24-month-old control (vehicle-treated) gpt delta mice were 1.14 ± 0.22 × 10(-5) and 1.00 ± 0.20 × 10(-5), respectively, which are significantly higher than that observed for the control 3-month-old (young) mice (0.59 ± 0.13 × 10(-5)) in our previous studies, indicating that spontaneous mutation in the lung increases with age. The mutant frequencies in 11- and 24-month-old mice treated with benzo [a] pyrene were 1.5- and 2.3-fold, respectively, that of the age-matched control mice, and 4.3-fold that of the 3-month-old mice in our previous studies. Analysis of mutation spectra showed that both G:C to A:T transitions and G:C to T:A transversions were predominant in the lungs of control mice at all ages. In benzo [a] pyrene-treated mice in our previous studies, G:C to T:A transversions were the predominant type of mutation (55 %) at 3 months. Here we found that their frequency was dramatically reduced to 18 % by 24 months, and the G:C to A:T transitions became the predominant type of mutation in 24-month-old mice (41 % [16 % at CpG sites]).
conclusionsOur findings suggest that susceptibility to benzo[a]pyrene is highest in young mice and is elevated again in old age. The elevation of G:C to A:T transitions was observed following benzo [a] pyrene administration in the lungs of aged mice, and accelerated cytidine deamination is speculated to contribute to this elevation.
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