Induction of CYP1A1 and NADPH quinone oxidoreductase (QR) with concomitant attenuation of CYP2B1 in the lung: effects of paving asphalt fume exposure.
Ma-JYC; Frazer-D; Barger-MW; Rengasamy-A; Hubbs-AF; Kane-E; Batteli-L; Tomblyn-S; Stone-S; Castranova-V
FASEB J 2002 Mar; 16(5):A962
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 (approximately 105 degrees C, approximately 20 mg/m3, 3.5h or 6h/day for 5 days). Lung microsomes and cytosol were isolated. The activities for P-4S0 isozymes (CYP1A1 and CYP2B1) 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 CYP1A1, but markedly reduced CYP2B1 levels and activity in the lung. By immunofluorescence, CYP1A1 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 CYP1A1 and QR with the concomitant attenuation of CYP2B1 after asphalt fume exposure may alter P AH metabolism leading to potential carcinogenicimutagenic effects.
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
NIOSH, HELD, 1095 Willowdale Road, Morgantown, WV 26505
Work Environment and Workforce: Mixed Exposures
The FASEB Journal, Experimental Biology 2002, New Orleans, Louisiana, April 20-24, 2002