Effects of asphalt fume exposure on the pulmonary cytochrome P450 systems.
Ma-JY; Frazer-D; Barger-MW; Tomblyn-S; Stone-S; Robinson-VA; Castranova-V
Toxicologist 2001 Mar; 60(1):427
Asphalt fumes are complex mixtures of aerosols and vapors containing various organic compounds, including polycyclic aromatic hydrocarbons (PAHs). The present study was carried out to determine the acute pulmonary inflammatory responses and the alteration of cytochrome P450 (P450) metabolism in rats exposed to asphalt fume by inhalation. Rats were exposed to air or asphalt fume generated at paving temperature (-150 C, -15 mg/m^3, 5 days, for either 3.5 h/day or 6h/day). To assess the inflammatory responses, differential cell counts, acellular LDH and protein content of the lavage fluid were determined. Chemiluminescence generation and the secretion of TNF-alpha and IL-1 were monitored to assess alveolar macrophage (AM) function. Microsomes were isolated by differential centrifugation of lung homogenate. The protein level and activity of P450 isozymes, CYP1A1 and CYP2B1, were determined to assess the effect of asphalt fume exposure of P450 systems. CYP2B1 and CYP1A1 activities were monitored by measuring O-dealkylation of 7-pentoxyresorufin and 7-ethoxyresorufin, respectively. The data show that asphalt fume exposure did not cause neutrophil infiltration, alter LDH and protein content, or affect AM function. These results suggest that asphalt fume exposure did not induce acute pulmonary inflammation. However, asphalt fume exposure significantly altered pulmonary P450 activity. Microsomes isolated from asphalt fume-exposed rats exhibited a concentration-dependent increase in CYP1A1 activity, while CYP2B1 activity was not significantly affected. Western blot analysis shows that exposure of rats to asphalt fume reduced microsomal CYP2B1 level, but significantly increased CYP1A1 level in comparison to the control. These results demonstrate that exposure of rats to paving asphalt fume significantly induced CYP1A1 activity and protein level in the lung. Such changes may alter PAH metabolism and lead to increased pulmonary susceptibility to potential toxic effects of PAHs.
Asphalt-fumes; Exposure-levels; Pulmonary-system; Aerosols; Vapors; Laboratory-animals; Toxic-effects
Mixed Exposures; Pulmonary System Disorders
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California