Diesel exhaust-induced airway hyperresponsiveness in c-Ha-ras transgenic mice.
Recently the quantity of diesel exhaust (DE) emissions, which contain a variety of chemicals and can induce pulmonary carcinoma in animals, has been increasing in Japan. To assess the toxicity of DE, we evaluated airway hyperresponsiveness after exposure to DE in the rasH2 (CB6F1-TgHras2) mouse, which carries c-Ha-ras genes and shows marked sensitivity to treatment with various genotoxic carcinogens such as methylnitrosourea and dimethylbenzanthracene. We exposed rasH2 mice (n=18) and their nontransgenic littermates (n=19) to room air or 3 mg/m(3) DE for 4 weeks, measured their respiratory resistance (Rrs) during inhalation of acetylcholine (ACh; 0.005, 0.01, 0.02, 0.04, 0.08, 0.16, 0.31, 0.63, 1.28, 2.5, 5, or 10 mg/ml) for 2 min, and calculated the provocative ACh concentration needed to cause a 50% increase (PC(150)) in Rrs. At all doses of ACh, Rrs was significantly higher (P<0.05) in rasH2 mice exposed to DE than in those exposed to room air. In addition, Rrs in the DE-exposed rasH2 animals was significantly higher (P<0.05) at 0.16, 0.31, and 0.63 mg/ml ACh than in DE-exposed nontransgenic littermates. The PC(150) (mean+/-standard error) of DE-exposed rasH2 mice was 3.4+/-1.9 mg/ml, that in rasH2 mice exposed to room air was 10.6+/-2.5 mg/ml, and that in DE-exposed nontransgenic animals was 10.9+/-3.7 mg/ml. In conclusion, DE causes airway hyperresponsiveness in rasH2 mice and may induce the expression of c-Ha-ras genes.
Birumachi
J
J
Japan Science and Technology Corporation, 4-1-8 Hon-cho, Kawaguchi, Saitama 332-0053, Japan. birumachi.junichi@nies.go.jp
Suzuki
A K
AK
Itoh
K
K
Hioki
K
K
Maruyama
C
C
Ohnishi
Y
Y
D000109:Acetylcholine; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001835:Body Weight; D016084:Bronchoconstriction; D015870:Gene Expression; D011905:Genes, ras; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012130:Respiratory Hypersensitivity / Q000209:etiology* / Q000503:physiopathology; D013997:Time Factors; D014139:Tracheostomy; D001335:Vehicle Emissions / Q000633:toxicity*
D001335:Vehicle Emissions; D000109:Acetylcholine