In vivo mutagenesis induced by benzo[a]pyrene instilled into the lung of gpt delta transgenic mice
In vivo mutagenesis induced by benzo[a]pyrene instilled into the lung of gpt delta transgenic mice
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DOI：
10.1002/em.20098
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发表时间：
2005-05-01
影响因子：
2.8
通讯作者：
Aoki, Y
中科院分区：
文献类型：
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作者：
Hashimoto, AH;Amanuma, K;Aoki, Y
苯并[a]芘（B[a]P）是一种普遍存在的空气污染物，其致突变性已通过口服和腹腔内给药的实验动物进行了评价。在这项研究中，肺，空气污染物的靶器官，诱变后，检查单intrichheal滴注0-2毫克B[a]P到gpt δ转基因小鼠。肠内注射B[a]P导致gpt突变频率的统计学显著性和剂量依赖性增加，如通过6-硫代鸟嘌呤选择测量的。B[a]P剂量为0.5、1和2环时的突变频率分别是未给药小鼠中观察到的频率（0.60 +/- 0.13 x 10（-5））的2.8、4.2和6.8倍。由B[a]P处理诱导的最常见的突变是G：C -> T：A颠换，这是其他模型中B[a]P诱变的特征，以及G：C碱基对的单碱基缺失。为了表征gpt基因中B[a] P诱导突变的热点，我们分析了突变的G：C碱基对附近的序列。以核苷酸序列C（G）、C（G）和C（G）为中心的碱基是B[a] P最常见的靶位。我们的研究结果表明，向gpt delta小鼠气管内滴注B[a]P可导致肺中gpt突变频率呈剂量依赖性增加，诱导的主要突变是G：C-T：A颠换。Environ.摩尔变异体45：365-373，2005. (c)2005 Wiley-Liss，Inc.
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 ring were 2.8, 4.2, and 6.8 times higher than the frequency seen in nontreated mice (0.60 +/- 0.13 x 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) under barT, C (G) under barA, and C (G) under barG 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. 45:365-373, 2005. (c) 2005 Wiley-Liss, Inc.