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Alteration of pulmonary cytochrome P-450 system by diesel exhaust particles.
Ma-JYC; Rengasamy-A; Barger-MW; Kane-E; Ma-JKH; Castranova-V
Toxicology 2001 Jul; 164(1-3):119
The adverse health effects of diesel exhaust particles (DEP) including genotoxicity have been attributed to absorbed polycyclic aromatic hydrocarbons (PAHs) on the particles. It has been prosposed that these compounds require bioactivation by cytochrome P-450 (CYP) to exert carcinogenicity. The objective of this study was to determine the effect of DEP exposure on CYP system in rat lung microsomes. Rats were intratracheally instilled with DEP or carbon black (CB) at 5.15 or 35 mg/kg. and the metabolic activity of CYP evaluated at various times post-exposure by measuring CYP1A1 and CYP2B1 protein levels. CYP isozyme activities, and glutathione S-transferase (GST) activity. The results show that DEP or CB exposure significantly reduced GST activity of the lung in a dose-dependent manner compared to the control. At 3 days post-exposure, high exposure doses (15 and 35 mg/kg) of DEP and CB significantly reduced CYP2B1 activity and protein level. In contrast, the CYP1A1 level and activity were significantly induced by DEP at all exposure doses but not by CB. At 35 mg/kg DEP, the induction of CYP1A1 was maximal at 1 day post-exposure then slowly decreased, but remained above the control level at 3 and 7 days post-exposure. These results suggest that DEP may have dual effects on the pulmonary metabolic system: an induction of CYP1A1 by the organic components and a reduction of CYP2B1 and GST activities by the carbon core. DEP exposure significantly altered the metabolic activity of cytochrome P-450 in the lung, which may lead to DEP induced toxicity carcinogenicity.
Diesel-exhausts; Genotoxic-effects; Hydrocarbons; Carcinogenicity; Exposure-levels; Proteins; Pulmonary-system; Polycyclic-aromatic-hydrocarbons; Bioactivation; Carcinogenesis; Carcinogens; Laboratory-animals; Animals; Animal-studies
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