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Induction of CYP1A1 and NADPH quinone oxidoreductase (QR) with concomitant attenuation of CYP2B1 in the lung: effects of paving asphalt fume exposure.

Authors
Ma-JYC; Frazer-D; Barger-MW; Rengasamy-A; Hubbs-AF; Kane-E; Batteli-L; Tomblyn-S; Stone-S; Castranova-V
Source
FASEB J 2002 Mar; 16(5):A962
NIOSHTIC No.
20023050
Abstract
Polycyclic aromatic hydrocarbons (PAHs) in asphalt fumes require bioactivation by cytochrome P-4S0 to exert toxic/carcinogenic effects. Exposure to asphalt fume may alter phase I (P-4S0) and phase II (QR and GST) enzymes in the lung. The objective of this study was to evaluate this hypothesis in a rat model. Rats were exposed to air or asphalt fume generated at paving temperature (-ISO.C, -20 mg/m3, 3.Sh or 6hJday for S days). Lung microsomes and cytosol were isolated. The activities for P-4S0 isozymes (CYPI Al and CYP2Bl) and phase II enzymes (QR and GST) were monitored. Protein levels were determined by Western blot analysis. The results show that asphalt fume exposure significantly induced the activity and protein levels of CYP1Al, but markedly reduced CYP2Bl levels and activity in the lung. By immunofluorescence, CYPI Al induction was localized in airways, blood vessels, and alveoli. Cytosolic QR activity was significantly elevated after asphalt fume exposure, whereas, GST activity was not affected by the exposure. This induction of CYPI Al and QR with the concomitant attenuation of CYP2Bl after asphalt fume
Keywords
Polycyclic-aromatic-hydrocarbons; Asphalt-fumes; Bioactivation; Toxic-effects; Animal-studies; Protective-measures; Liver-enzymes; Carcinogens; Fumes; Exposure-levels; Carcinogenesis; Air-samples; Lung-cells; Lung-function; Pulmonary-system
Contact
NIOSH, HELD, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
FAJOEC
Publication Date
20020322
Document Type
Abstract; Conference/Symposia Proceedings
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Issue of Publication
5
ISSN
0892-6638
NIOSH Division
HELD
Priority Area
Work Environment and Workforce: Mixed Exposures
Source Name
The FASEB Journal, Experimental Biology 2002, New Orleans, Louisiana, April 20-24, 2002
State
WV; LA
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