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Effects of paving asphalt fume exposure on genotoxic and mutagenic activities in the rat lung.

Authors
Zhao-HW; Yin-XJ; Frazer-D; Barger-MW; Siegel-PD; Millecchia-L; Zhong-BZ; Tomblyn-S; Stone-S; Ma-JKH; Castranova-V; Ma-JYC
Source
Mutat Res 2004 Feb; 557(2):137-149
NIOSHTIC No.
20024194
Abstract
Asphalt fumes are complex mixtures of aerosols and vapors containing various organic compounds, including polycyclic aromatic hydrocarbons (PAHs). Previously, we have demonstrated that inhalation exposure of rats to asphalt fumes resulted in dose-dependent induction of CYP1A1 with concomitant down-regulation of CYP2B1 and increased phase II enzyme quinone reductase activity in the rat lung. In the present study, the potential genotoxic effects of asphalt fume exposure due to altered lung microsomal enzymes were studied. Rats were exposed to air or asphalt fume generated under road paving conditions at various concentrations and sacrificed the next day. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage and examined for DNA damage using the comet assay. To evaluate the systemic genotoxic effect of asphalt fume, micronuclei formation in bone marrow polychromatic erythrocytes (PCEs) was monitored. Lung S9 from various exposure groups was isolated from tissue homogenates and characterized for metabolic activity in activating 2-aminoanthracene (2-AA) and benzo[a]pyrene (BaP) mutagenicity using the Ames test with Salmonella typhimurium YG1024 and YG1029. This study showed that the paving asphalt fumes significantly induced DNA damage in AM, as revealed by DNA migration in the comet assay, in a dose-dependent manner, whereas the micronuclei formation in bone marrow PCEs was not detected even at a very high exposure level (1733 mg h/m3). The conversion of 2-AA to mutagens in the Ames test required lung S9-mediated metabolic activation in a dose-dependent manner. In comparison to the controls, lung S9 from rats exposed to asphalt fume at a total exposure level of 47933 mg h/m3 did not significantly enhance 2-AA mutagenicity with either S. typhimurium YG1024 or YG1029. At a higher total asphalt fume exposure level (115063 mg h/m3), S9 significantly increased the mutagenicity of 2-AA as compared to the control. However, S9 from asphalt fume-exposed rats did not significantly activate the mutagenicity of BaP in the Ames test. These results show that asphalt fume exposure, which significantly altered both phases I and II metabolic enzymes in lung microsomes, is genotoxic to AM and enhances the metabolic activation of certain mutagens through altered S9 content.
Keywords
Asphalt-fumes; Aerosols; Vapors; Animal-studies; Animals; Polycyclic-aromatic-hydrocarbons; Polycyclic-hydrocarbons; Mutagenesis; Mutagenicity; Genotoxic-effects; Laboratory-animals
Contact
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
CODEN
MUREAV
Publication Date
20040201
Document Type
Journal Article
Email Address
jym1@cdc.gov
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0027-5107
NIOSH Division
HELD
Source Name
Mutation Research
State
WV
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