Hashimoto Akiko H, Amanuma Kimiko, Hiyoshi Kyoko, Sugawara Yoshiki, Goto Sataro, Yanagisawa Rie, Takano Hirohisa, Masumura Ken-ichi, Nohmi Takehiko, Aoki Yasunobu
Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Environ Mol Mutagen. 2007 Oct;48(8):682-93. doi: 10.1002/em.20335.
Diesel exhaust (DE) is a major airborne pollutant of urban areas. It contains various polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs. In this study, gpt delta mice were treated with inhalation of 1 or 3 mg m(-3) DE, or a single intratracheal instillation of diesel exhaust particles (DEP) or DEP extract. In the lungs of mice treated with inhalation of 3 mg m(-3) DE for 12 weeks, the mutant frequency (MF) was 3.2-fold higher than that of the control group (1.90 x 10(-5) and 0.59 x 10(-5), respectively). An instillation of DEP and DEP extract resulted in a significant dose-dependent linear increase in MF. In mice treated with 0.5 mg DEP and 0.2 mg DEP extract, the MFs were 3.0- and 2.7-fold higher than that of the control group, respectively. The mutagenic potency (MF mg(-1)) of DEP extract (5.6 x 10(-5)) was double that of DEP (2.7 x 10(-5)), suggesting that the mutagenicity of the latter is derived primarily from compounds in the extract, which itself is responsible for ca. 50% of the weight of DEP. G:C-->A:T transitions were the predominant gpt mutation induced by all three treatments and G:C-->T:A transversions were induced by DEP and DEP extract. Guanine bases centered in nucleotide sequences such as GGA, TGA, CGG, and CGT were the major mutation targets of all three treatments. Thus, our results suggest that the mutagens contained in DEP such as PAH and nitrated PAHs induce mutations and may be responsible for carcinogenesis caused by inhalation of DE.
柴油废气（DE）是城市地区主要的空气污染物。它含有多种多环芳烃（PAH）和硝化多环芳烃。在本研究中，对gpt delta小鼠进行如下处理：吸入1或3 mg/m³的DE，或单次气管内滴注柴油废气颗粒（DEP）或DEP提取物。在吸入3 mg/m³的DE持续12周的小鼠肺中，突变频率（MF）比对照组高3.2倍（分别为1.90×10⁻⁵和0.59×10⁻⁵）。滴注DEP和DEP提取物导致MF呈显著的剂量依赖性线性增加。在用0.5 mg DEP和0.2 mg DEP提取物处理的小鼠中，MF分别比对照组高3.0倍和2.7倍。DEP提取物的诱变效力（MF mg⁻¹）（5.6×10⁻⁵）是DEP（2.7×10⁻⁵）的两倍，这表明后者的诱变性主要源自提取物中的化合物，该提取物本身约占DEP重量的50%。G:C→A:T转换是所有三种处理诱导的主要gpt突变，而G:C→T:A颠换由DEP和DEP提取物诱导。以GGA、TGA、CGG和CGT等核苷酸序列为中心的鸟嘌呤碱基是所有三种处理的主要突变靶点。因此，我们的结果表明，DEP中含有的诱变剂如PAH和硝化多环芳烃可诱导突变，可能是吸入DE导致致癌的原因。
