RT Journal Article
SR Electronic
T1 Metabolic Capabilities of CYP2F2 with Various Pulmonary Toxicants and Its Relative Abundance in Mouse Lung Subcompartments
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 510
OP 519
VO 296
IS 2
A1 Michael A. Shultz
A1 Dexter Morin
A1 Ai-Min Chang
A1 Alan Buckpitt
YR 2001
UL http://jpet.aspetjournals.org/content/296/2/510.abstract
AB 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 relevantK m values (21.5 and 3.7 μM, 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.