Pulmonary metabolism of epoxides.

Activities of epoxide hydrase (EH) and glutathione S-transferase (GST) have been measured in pulmonary tissue from several species. On the basis of total organ activity, pulmonary tissue has less capacity than liver tissue to metabolize epoxides. Pulmonary EH and GST appear to be refractory to induction by typical agents. Rat pulmonary GST will conjugate a variety of epoxides, but K-region epoxides are metabolized at lower rates than alkene oxides. In the isolated perfused rabbit lung, benzo (a) pyrene-4,5-oxide (BPO) is metabolized by EH and GST at similar initial rates, but EH activity is lost after a few minutes, apparently owing to inadequate local substrate levels. GST from rabbit lung cytosol has been separated by chromatographic methods into six peaks of enzymic activity (toward 1-chloro-2,4-denitrobenzene). Of these peaks, all six metabolized BPO and two metabolized styrene oxide. Although EH and GST are less active in lung than in liver, pulmonary metabolism of epoxides is important because this tissue must be able to protect itself from arene oxides generated by pulmonary oxidative metabolism of polycyclic aromatic hydrocarbons.