Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust.
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.
Hashimoto
Akiko H
AH
Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Amanuma
Kimiko
K
Hiyoshi
Kyoko
K
Sugawara
Yoshiki
Y
Goto
Sataro
S
Yanagisawa
Rie
R
Takano
Hirohisa
H
Masumura
Ken-ichi
K
Nohmi
Takehiko
T
Aoki
Yasunobu
Y
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*
D001335:Vehicle Emissions; D007041:Hypoxanthine Phosphoribosyltransferase