Diesel exhaust particle-induced alterations of pulmonary phase I and phase II enzymes of rats.
Rengasamy-A; Barger-MW; Kane-E; Ma-JKH; Castranova-V; Ma-JYC
J Toxicol Environ Health, A 2003 Jan; 66(2):153-167
Although diesel exhaust particles (DEP) are known to produce pulmonary disorders, the xenobiotic metabolic pathways associated with DEP detoxification and bioactivation remain unclear. In this study, the effect of acute exposure of DEP on phase I and phase II enzymes of rat lung was investigated. Intratracheal administration of DEP produced an induction of cytochrome P-450 (CYP) 1A1 enzyme protein and activity at 1 d postexposure, with the enzyme level returning to control at 5 d postexposure. On the other hand, carbon black (CB), a particle control, did not show any induction of CYP1A1 protein or enzyme activity. However, both DEP and CB significantly decreased CYP2B1 protein and enzyme activity at 1 d postexposure. The decrease in CYP2B1 enzyme protein and activity by DEP or CB treatment was observed up to 7 d postexposure. DEP and CB treatments also significantly attenuated glutathione S-transferase (GST)-pi protein at 1 d postexposure. Both DEP and CB at 35 mg/kg significantly decreased the activities of GST and catalase at 1 and 7 d postexposure. DEP, but not CB, significantly induced quinone reductase (QR) activity at 7 d postexposure. This study suggests that DEP may induce CYP1A1 and QR enzymes via a chemical effect, while the carbonaceous core may be involved in the attenuation of CYP2B1, GST, and catalase proteins and enzyme activities.
Diesel-exhausts; Pulmonary-disorders; Animal-studies; Animals; Laboratory-animals; Enzymes; Proteins; Exposure-levels; Exhaust-gases; Combustion-gases; Combustion-products; Particulates
Jane Y. C. Ma, PhD, Pathology and Physiology Research Branch, Health Effects Laboratory Division, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505, USA
Work Environment and Workforce: Mixed Exposures
Journal of Toxicology and Environmental Health, Part A: Current Issues