title: Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust.
abstract: 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.
authors: Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
authors: Akiko H
authors: AH
authors: Hashimoto
authors: Kimiko
authors: K
authors: Amanuma
authors: Kyoko
authors: K
authors: Hiyoshi
authors: Yoshiki
authors: Y
authors: Sugawara
authors: Sataro
authors: S
authors: Goto
authors: Rie
authors: R
authors: Yanagisawa
authors: Hirohisa
authors: H
authors: Takano
authors: Ken-ichi
authors: K
authors: Masumura
authors: Takehiko
authors: T
authors: Nohmi
authors: Yasunobu
authors: Y
authors: Aoki
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D009154:Mutation; D016133:Polymerase Chain Reaction; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D001335:Vehicle Emissions; D007041:Hypoxanthine Phosphoribosyltransferase