Qualitative and quantitative changes in cytochrome p‐450‐dependent xenobiotic metabolism in pulmonary microsomes and isolated clara cell populations derived from ozone‐exposed rats

Abstract

The effect of a prolonged ozone exposure (1.6 mg ozone/m³; 7 d; 24 bid) on pulmonary cytochrome P‐450‐dependent xenobiotic metabolism was studied both in whole rat lung as well as in isolated bronchiolar Clara cell preparations. Ozone exposure was demonstrated to result in significant quantitative but also qualitative changes. All components of the pulmonary microsomal electron transport system appeared to be significantly increased in the lungs of exposed animals both per lung and per gram lung, although increases were no longer observed when expressed per milligram microsomal lung protein. Remarkably, it was demonstrated that the increases in the components of the pulmonary cytochrome P‐450 system were not accompanied by a concomitant increase in all cytochrome P‐450‐dependent substrate conversions.

In whole‐lung microsomes ethoxycoumarin O‐deethylase and ethoxyresorufin O‐deethylase activities were unchanged or even significantly reduced when expressed per lung, per gram lung, per milligram microsomal protein, or per picomole cytochrome P‐450. In contrast to these observations, pentoxyresorufin O‐dealkylation appeared to be significantly increased upon ozone exposure when expressed per lung, per gram lung, and even per picomole cytochrome P‐450.