Altered expression of lung cytochrome P450 3A1 in rat after exposure to sulfur mustard

Expression of cytochromes P450 (CYP) and glutathione S-transferases in the lung may be affected by inhaled pollutants. We have investigated the effect of sulfur mustard on the expression of CYP 1A1, 2B1, 2E1 and 3A1, as well as of alpha-, mu- and pi -glutathione S-transferases in rat lung. Sulfur mu stard (0.025, 0.05 or 0.1 mg/kg) or its vehicle was administered to anaesth etized animals by intratracheal injection. Expression of CYP and glutathion e S-transferases was analysed 24 hr after administration of the vesicant wa rfare using western blotting. Preservation of airway epithelium integrity a fter animal exposure to sulfur mustard was confirmed by histological examin ation of tracheal and lung tissues from control and treated animals. Consti tutive levels of CYP 2B1 and 3A1 proteins were found in lung tissue from co ntrol rats, whereas CYP 1A1 and 2E1 proteins were not detected. Animal expo sure to sulfur mustard enhanced CYP 3A1 protein levels by 80 to 103%. In co ntrast, exposure to sulfur mustard neither modified CYP 2B1 expression, nor led to detectable expression of CYP 1A1 or 2E1. Constitutive levels of alp ha-, mu- and pi -glutathione S-transferase proteins were found in lung tiss ue from control rats. Exposure to sulfur mustard had no effect on expressio n of either of the glutathione S-transferases. Our results show that intrat racheal exposure to sulfur mustard selectively increases CYP 3A1 expression in rat lung. Taking into account the major role of CYP of the 3A family in the metabolism of drugs, up-regulation of CYP 3A1 by sulfur mustard might have important therapeutic consequences.