Cytochrome P450 1A1 and 2B1 in the rat lung: exposure to silica and inducers of xenobiotic metabolism.
Battelli-LA; Hubbs-AF; Simoskevitz-RD; Vallyathan-V; Bowman-L; Miles-PR
Toxicologist 1999 Mar; 48(1-S):97
Pulmonary exposure to respirable silica causes alveolar type 2 cell proliferation. Cytochrome P450 (CYP) is present in type 2 cells and increased levels of CYP 1A1 are reported in silicotic rats. Because carcinogen activation by CYPIAI may contribute to human lung cancer and because silica is often present in occupational mixed dust exposures, we hypothesized that new type 2 cells in silicosis are potential sites of CYP 1 Al induction and carcinogen activation. Male Sprague-Dawley rats received intratracheal silica (20mg) or vehicle (saline). The silicotic and control rats were then exposed to inducers of xenobiotic metabolism by the intraperitoneal injection of Phenobarbital (PB), f3-naphthoflavone (NF), NF and PB, or vehicle (com oil). 7ethoxyresorufin (ER)-O-dethylase (EROD) and 1-ethoxycoumarin (EC)-O-deethylase (ECOD) activities were increased by NF but unaffected by PB. Morphometrically, the number of cells expressing immunoreactive CYP 2BI was not significantly affected by silica, NF, and/or PB. CYP IA1 positive airway and alveolar epithelial cells were absent in controls, present after NF exposure but not significantly increased by PB or silica. Although we had hypothesized that induction of type 2 cells would lead to more xenobiotically active cells in silicotic rats, NF-exposed silicotic rats had significantly less EROD activity than NF-exposed control rats. We conclude that the new type 2 cells of silicosis were not a major site of 1Al induction in combined, exposures in this rat model.
Animal-studies; Animals; Laboratory-animals; Statistical-analysis; Chemical-analysis; Analytical-chemistry; Analytical-methods; Respiratory-system-disorders; Respiratory-irritants; Pulmonary-disorders; Pulmonary-system-disorders; Carcinogens; Cancer; Quartz-dust; Silica-dusts; Silicates; Respirable-dust; Dust-particles; Dust-exposure; Dust-analysis
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana