Genetic and Environmental Regulation of Aryl Hydrocarbon Hydroxylase in Man: Studies with Liver, Lung, Placenta, and Lymphocytes

Abstract

Properties and response smoking of aryl hydrocarbon hydroxylase (AHH) activity in various human tissues are reviewed. In the placenta, induction of AHH by smoking can be demonstrated unequivocally. AHH activity in lung samples is variable, but the relation to current or past smoking i s unclear. The effect of cigarette smoking can be readily shown in the rate of antipyrine elimination, although there i s no change in AHH activity in liver biopsy samples. The reason for this discrepancy i s not known. In peripheral lymphocytes a sort of "memory-effect" of cigarette smoking i s retained even after culturing, the nature of this phenomenon remaining unclear. Furthermore, there seem to be many factors affecting AHH induction i n peripheral lymphocytes i n culture. These data suggest that regulation of AHH activity and induction i s tissuespecific, i.e. no systemic regulation is discernible. It i s also possible that the P-450 isozyme composition in some tissues masks the induction.Reasons for discrepancies between animal and human data are not clear; however, genuine biological differences and technical difficulties i n human studies can be postulated.

The effect of cigarette smoking on 7‐ethoxyresorufin O‐deethylase and other monooxygenase activities in human liver: analyses with monoclonal antibodies.

“…However, animal experiments have demonstrated that the exposure to cigarette smoke does not induce hepatic xenobiotic metabolism, whereas the same treatment induces extrahepatic xenobiotic metabolism (for ref. see Pelkonen, 1976;Pelkonen et al, 1984;Vahakangas et al, 1983). The few available studies with human tissues have not yielded definitive results (Boobis et al, 1980;Pelkonen et al, 1975;Vahakangas et al, 1983).…”

“…Pelkonen, 1976;Pelkonen et al, 1984). It is thought that the increase in the plasma elimination of a number of drugs is due to the induction of hepatic drug-metabolizing enzymes, but unequivocal proof in man has not been provided.…”

Human Placental Xenobiotic and Steroid Biotransformations Catalyzed By Cytochrome P450, Epoxide Hydrolase, and Glutathione S-Transferase Activities and Their Relationships to Maternal Cigarette Smoking

“…Once established, the AHH levels seem to persist for some weeks after removing the inducing stimulus [35]. In contrast to hepatic microsomes, placental microsomes with high AHH activity do not contain increased concentrations of the components for electron transport When compared to other human tissues, placenta responds sensitively to cigarette smoking [41,421. The dose-response curve between the number of cigarettes smoked daily and AHH activity is sigmoidal [43].…”

The effect of cigarette smoking on drug metabolism in the liver and placenta: the use of cotinine in verifying smoking status

“…The elimination of several drugs is enhanced and the metabolism of polycyclic aromatic hydrocarbons (PAH) in certain human tissues is increased by cigarette smoking (1)(2)(3)(4).…”

“…The microsomal xenobiotic-metabolising system in the liver responds also to cigarette smoking, although to a lesser extent (1,3,4). However, estimation of the level of exposure to inducing agents, for instance cigarette smoke, is not an easy task.…”