The Effect of Cigarette Smoke on Aryl Hydrocarbon Hydroxylase Activity and Cytochrome P450 Content in Rat Liver and Lung Microsomes

Abstract

Levels of activity of the enzyme aryl hydrocarbon hydroxylase and cytochrome P450 have been estimated in lung and liver of rats exposed to graded doses of cigarette smoke and in human bronchial mucosa of smokers, non-smokers and patients with lung cancer. Exposure of rats to smoke of four cigarettes increased both hepatic and pulmonary aryl hydrocarbon hydroxylase activity. Exposure to smoke of four cigarettes daily for seven and 14 days did not result in higher aryl hydrocarbon hydroxylase levels in the liver than one day’s exposure, but in the lung longer exposures caused greater increases in enzyme activity. Injection of benzo(a)pyrene at two dose levels caused a much greater increase in both 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 both 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, non-smokers and cancer patients, only one was found to have 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.

The effect of a single treatment with cigarette smoke on the blood levels and hemodynamic effects of propranolol in rats

“…The results of the positive control experiments of our study demonstrated that cigarette smoke enhanced the metabolism of zoxazolamine but not of pentobarbital. This finding is in agreement with the results obtained by some other investigators (18,20). It is clear from our findings (Tables I and mthat cigarette smoke did not affect aliphatic hydroxylase activity either immediately or 24 h after the exposures.…”

“…The first i.v, injection of isoproterenol elicited significant reduction of the mean arterial blood pressure in all groups. The~-blockade effect of propranolol was evident in the control group at 10 and 20 min time intervals and was effective throughout the DISCUSSION \ There is significant evidence from the literature indicating that substances in cigarette smoke induce liver microsomal enzymes which increase the metabolism of certain drugs in humans (8,17) and in small laboratory animals (18). Measurement of the duration of action of both pentobarbital and zoxazolamine are simple tests commonly used to detennine enzyme induction in vivo (19).…”

Effects of Tobacco Smoking and Nicotine on Cancer Treatment

“…Cigarette smoking is one of the environmental factors that can influence the activity of several CYP enzymes. In 1976, researchers reported that injection of benzo[a]pyrene, which is formed as a result of cigarette smoking, caused a great increase in both liver weight and CYP content in rats . This induction may alter the efficacy of many drugs by decreasing their parent drug exposure and may also increase the risk of cancer by enhancing the metabolic activation of procarcinogens.…”

Smoking and Lung Cancer

“…W połowie wieku dwa badawcze zespoły, niezależnie od siebie, udowodniły związek między paleniem tytoniu a ryzykiem zachoro-wania na raka płuca. Zależność ta potwierdziła się w następnych latach w licznych badaniach epidemiologicznych i doświadczalnych [3][4][5][6].…”