EFFECT OF CIGARETTE-SMOKE ON ARYL-HYDROCARBON HYDROXYLASE-ACTIVITY AND CYTOCHROME P450 CONTENT IN RAT-LIVER AND LUNG MICROSOMES

Levels of activity of the enzyme aryl hydrocarbon hydroxylase and cytochrome P450 were estimated in lung and liver of rats exposed to graded doses of cigarette smoke and human bronchial mucosa of smokers, nonsmokers and patients with lung cancer. Exposure of rats to smoke of 4 cigarettes increased hepatic and pulmonary aryl hydrocarbon hydroxylase activity. Exposure to smoke of 4 cigarettes daily for 7 and 14 days did not result in higher aryl hydrocarbon hydroxylase levels in the liver than 1 day''s exposure, but in the lung longer exposures caused greater increases in enzyme activity. Injection of benzo(a)pyrene at 2 dose levels caused a greater increase in liver and lung aryl hydrocarbon hydroxylase than smoking. The lower dose maximally stimulated the enzyme in both organs. The changes in aryl hydrocarbon hydroxylase activity were accompanied by significant increases in liver weight and the cytochrome P450 content of liver microsomes but the increase in cytochrome P450 did not parallel those in aryl hydrocarbon hydroxylase activity. Of 40 surgical and autopsy specimens of human lung and tracheal mucosa from smokers, nonsmokers and cancer patients, only 1 had detectable aryl hydrocarbon hydroxylase activity. The relationship between aryl hydrocarbon hydroxylase induction by cigarette smoke in human tissues and the development of bronchogenic carcinoma in smokers remains unclear.