An Evaluation of the Comparative Metabolism and Kinetics of 1-Nitropyrene by Rabbit, Rat, and Hamster Tracheal Epithelial Cells

Abstract

The comparative metabolism of 1-nitropyrene was studied in isolated rabbit, rat, and hamster tracheal epithelial cells commonly used in neoplastic transformation assays. The maximum total metabolite production for all species was attained at 2.0 × 106 cells and 4 hr incubation, with no significant increase after 20 hr. The majority of the metabolites produced by tracheal epithelial cells from each species were released into the surrounding medium. The metabolites retained by tracheal epithelial cells were qualitatively identical to those identified in the medium but were present at lower concentrations. The apparent Km for the metabolism of 1-nitropyrene by tracheal epithelial cells was in the order of rabbit (5.1 μM) < hamster (9.1 μM) < rat (13 μM). The apparent V/K value for the metabolism of 1-nitropyrene by tracheal epithelial cells was also in the order of rabbit (2.0 nmol/hr/mg protein) > hamster (1.6 nmol/hr/mg protein) > rat (0.48 nmol/hr/mg protein). Intrinsic clearance of the previously characterized mutagenic metabolites (3-OH-1-NAAP, K-DHD, 10-OH-1-NP, 1-AMP, and phenols 6- or 8-OH-1-NP) produced by tracheal epithelial cells at their approximate Km values also indicated that rabbit tracheal cells were more active in the production of these metabolites than either hamster or rat tracheal cells. Although the metabolism of 1-NP in isolated tracheal epithelial cells of these three species was qualitatively similar, rabbit tracheal cells are the most active in metabolizing 1-NP. These results are consistent with the possibility that tracheal epithelial cells may be a target tissue for NO2-PAHs carcinogenesis.