Carcinogenesis, Vol. 21, No. 4, 653-661,
April 2000
© 2000 Oxford University Press
Carcinogenesis |
Increase in mutation frequency in lung of Big Blue® rat by exposure to diesel exhaust
1 Environmental Health Sciences Division,
2 Chemical Exposure and Health Research Team and
3 Research Team for Health Effects of Air Pollutants, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-0053, Japan and
4 Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi, Inage, Chiba 263-8522, Japan
Exposure to diesel exhaust (DE) is known to cause lung tumors in rats. To clarify the mutagenicity of DE, we estimated mutant frequency (MF) and determined the mutation spectra in rat lung after exposure to DE using lambda/lacI transgenic rats (Big Blue® system). Male Big Blue® rats (6 weeks old) were exposed for 4 weeks to 1 or 6 mg/m3 DE, which contains suspended particulate matter. Control rats were maintained in filtered clean air. After exposure to 6 mg/m3 DE, MF in lung was 4.8-fold higher than in control rats (P < 0.01), but no increase in MF was observed in rats exposed to 1 mg/m3 DE. Sixty-nine mutants were identified after exposure to 6 mg/m3 DE. The major mutations were A:T
G:C (18 mutations) and G:CA:T (19 mutations) transitions. Remarkably, GT transversion of the lacI gene at site 221 was a hot-spot induced by exposure to DE, and there were complex mutations in which multiple mutations occurred in a single mutant, especially in the rats exposed to 6 mg/m3 DE. DNA adducts formed by DE were analyzed using a 32P-post-label TLC method and the amount of 8-hydroxydeoxyguanosine (8-OHdG) was measured using HPLC. Relative adduct level and amount of 8-OHdG were significantly increased in the rats exposed to 6 mg/m3 DE compared with the controls (3.0- and 2.2-fold, respectively; P < 0.01). The level of cytochrome P450 1A1 mRNA was shown by northern blot analysis to be significantly increased in the lungs of rats exposed to 6 mg/m3 DE (5.5-fold; P < 0.01). These results indicate that DE causes lesions in genomic DNA and acts as a mutagen in rat lung.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  V. M. Arlt 3-Nitrobenzanthrone, a potential human cancer hazard in diesel exhaust and urban air pollution: a review of the evidence Mutagenesis, November 1, 2005; 20(6): 399 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Vineis and K. Husgafvel-Pursiainen Air pollution and cancer: biomarker studies in human populations Carcinogenesis, November 1, 2005; 26(11): 1846 - 1855. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sorensen, R. P.F. Schins, O. Hertel, and S. Loft Transition Metals in Personal Samples of PM2.5 and Oxidative Stress in Human Volunteers Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1340 - 1343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Avogbe, L. Ayi-Fanou, H. Autrup, S. Loft, B. Fayomi, A. Sanni, P. Vinzents, and P. Moller Ultrafine particulate matter and high-level benzene urban air pollution in relation to oxidative DNA damage Carcinogenesis, March 1, 2005; 26(3): 613 - 620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Risom, M. Dybdahl, J. Bornholdt, U. Vogel, H. Wallin, P. Moller, and S. Loft Oxidative DNA damage and defence gene expression in the mouse lung after short-term exposure to diesel exhaust particles by inhalation Carcinogenesis, November 1, 2003; 24(11): 1847 - 1852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Pohjola, M. Lappi, M. Honkanen, L. Rantanen, and K. Savela DNA binding of polycyclic aromatic hydrocarbons in a human bronchial epithelial cell line treated with diesel and gasoline particulate extracts and benzo[a]pyrene Mutagenesis, September 1, 2003; 18(5): 429 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sorensen, H. Autrup, O. Hertel, H. Wallin, L. E. Knudsen, and S. Loft Personal Exposure to PM2.5 and Biomarkers of DNA Damage Cancer Epidemiol. Biomarkers Prev., March 1, 2003; 12(3): 191 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hatanaka, H. Yamazaki, R. Kizu, K. Hayakawa, Y. Aoki, M. Iwanari, M. Nakajima, and T. Yokoi Induction of cytochrome P450 1B1 in lung, liver and kidney of rats exposed to diesel exhaust Carcinogenesis, December 1, 2001; 22(12): 2033 - 2038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Bonvallot, A. Baeza-Squiban, A. Baulig, S. Brulant, S. Boland, F. Muzeau, R. Barouki, and F. Marano Organic Compounds from Diesel Exhaust Particles Elicit a Proinflammatory Response in Human Airway Epithelial Cells and Induce Cytochrome p450 1A1 Expression Am. J. Respir. Cell Mol. Biol., October 1, 2001; 25(4): 515 - 521. [Abstract] [Full Text] [PDF]
|
|