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Updated: Aug 8, 2026
Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity
Published on: January 6, 2015
Metabolic capabilities of CYP2F2 with various pulmonary toxicants and its relative abundance in mouse lung
M A Shultz1, D Morin, A M Chang
1Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis 95616, USA.
Abstract:
The tissue- and species-selective toxicity of a number of pulmonary toxicants has been attributed to the presence and distribution of activating enzymes with high k(cat) in target airways of susceptible species. The mouse is especially sensitive to a variety of metabolically activated lung toxicants. Recombinant CYP2F2 (mouse) was recently shown to effectively metabolize the species-selective pulmonary toxicant naphthalene. Here we show that the pulmonary toxicants 1-nitronaphthalene and 2-methylnaphthalene are metabolized readily with high k(cat) values (17.1 and 67.6 min(-1), respectively) to potentially cytotoxic intermediates at biologically relevant K(m) values (21.5 and 3.7 microM, respectively). Additionally, anthracene and benzo[a]pyrene are both metabolized by CYP2F2 (0.14 +/- 0.04 and 0.04 +/- 0.00 nmol/nmol/min, respectively), albeit at much lower rates. The levels of total CYP in mouse airways are considerably higher than those in parenchyma and trachea, and this is consistent with much higher rates of naphthalene metabolism in microsomal preparations from airways compared with the other subcompartments. The data suggest that CYP2F2 is a prominent cytochrome P450 in mouse lung that metabolizes a number of pulmonary toxicants. The presence of CYP2F2 may be important in the susceptibility of the mouse to metabolically activated pulmonary toxicants.
Insights
Mouse lung cytochrome P450 2F2 (CYP2F2) metabolizes key pulmonary toxicants like 1-nitronaphthalene and 2-methylnaphthalene. This enzyme’s presence in airways may explain mouse susceptibility to these harmful compounds.
Area of Science:
- Toxicology
- Biochemistry
- Pharmacology
Background:
- Pulmonary toxicant sensitivity varies by species and is linked to activating enzyme distribution.
- Mice show high susceptibility to metabolically activated lung toxicants.
- Mouse cytochrome P450 2F2 (CYP2F2) was previously identified as a naphthalene metabolizer.
Purpose of the Study:
- To investigate the metabolism of pulmonary toxicants by mouse CYP2F2.
- To determine the kinetic parameters for CYP2F2-mediated metabolism of specific toxicants.
- To correlate CYP2F2 levels in mouse lung with toxicant metabolism.
Main Methods:
- Recombinant mouse CYP2F2 was used to study the metabolism of 1-nitronaphthalene, 2-methylnaphthalene, anthracene, and benzo[a]pyrene.
- Kinetic parameters (k(cat) and K(m)) were determined for relevant substrates.
- Cytochrome P450 (CYP) levels were quantified in different mouse lung subcompartments (airways, parenchyma, trachea).
Main Results:
- CYP2F2 readily metabolized 1-nitronaphthalene and 2-methylnaphthalene at high rates (k(cat) values of 17.1 and 67.6 min(-1)) and biologically relevant concentrations (K(m) values of 21.5 and 3.7 microM).
- Anthracene and benzo[a]pyrene were also metabolized by CYP2F2, but at significantly lower rates.
- Total CYP levels were substantially higher in mouse airways compared to parenchyma and trachea, correlating with higher naphthalene metabolism rates in airways.
Conclusions:
- Mouse CYP2F2 is a prominent cytochrome P450 in the lung, capable of metabolizing various pulmonary toxicants.
- The high activity and specific distribution of CYP2F2 in mouse airways likely contribute to the species-specific susceptibility to certain metabolically activated lung toxicants.
