© 1990 Oxford University Press
research-article |
Hepatic Aryl Hydrocarbon Hydroxylase and Cytochrome P450 Induction following the Transpulmonary Absorption of TCDD from Intratracheally Instilled Particles
Department of Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School Piscataway, New Jersey 08854 *Graduate Program in Public Health, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School Piscataway, New Jersey 08854
Received December 27, 1989; accepted May 11, 1990
Hepatic Aryl Hydrocarbon Hydroxylase and Cytochrome P450 Induction following the Transpulmonary Absorption of TCDD from Intratracheally Instilled Particles. NESSEL, C. S., AMORUSO, M. A., UMBREIT, T. H., AND GALLO, M. A. (1990). Fundam. Appl. Toxicol. 15, 500-509. Inhalation of particles contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) will be an increasingly important route of human exposure in light of the increased utilization of municipal waste incineration and the resultant emission of contaminated materials into the environment. The potential for pulmonary absorption of the compound from respirable particles was assessed in the present study following the intratracheal instillation of TCDD (1) as a contaminant of gallium oxide particles and (2) in a corn oil vehicle. Groups of five female Sprague-Dawley rats received 0, 0.005, 0.055, 0.55, or 5.5 µg/kg TCDD in a single instillation and were euthanized 4 days later. Absorption was characterized by enzyme induction [aryl hydrocarbon hydroxylase (AHH) activity and total cytochrome P450] and histopathological examination of the liver. Induction of hepatic enzymes was dose-dependent with both treatment regimes. Up to an 18-fold increase in AHH and an 80% increase in cytochrome P450 were observed in treated animals. Induction was slightly higher when animals received TCDD in com oil than when animals received TCDD-contaminated particles and was relatively comparable to induction following oral exposure. Similar results were obtained when animals were treated with particles contaminated up to 4 weeks prior to instillation. Characteristics of TCDD-induced hepatotoxicity, including enlarged hepatocytes and fatty infiltration, were apparent in treated rats, but were not present in vehicle-instilled animals. These results indicate that systemic effects occur following pulmonary exposure to TCDD and that inhalation may be an important route Of exposure for TCDD.