Cigarette smoke, induction

Liu, C., Russell, R.M., and Wang, X.D., Exposing ferrets to cigarette smoke and a pharmacological dose of beta-carotene supplementation enhance in vitro retinoic acid catabolism in lungs via induction of cytochrome P450 enzymes, J. Nutr., 133, 173, 2003. 

Cigarette smoking may act as a promotor for lung cancer induction. 

Jansson T, Curvall M, Hedin A, et al. 1986. In vitro studies of biological effects of cigarette smoke condensate. II. Induction of sister chromatid exchanges in human lymphocytes by weakly acidic, semivolatile constituents. MutatRes 169 129-139. 

On the basis of a few reports, it is assumed that a "local vitamin A deficiency exists in meta- and dysplastic areas. Measurements of vitamin A concentrations in metaplastic areas of the respiratory epithelium and the cervix epithelium actually proved that vitamin A in comparison to the surrounding tissues was not found (Biesalski, 1996). Clearly one cannot say what is cause and effect. Studies carried out by Edes et al. (1991) confirm an induction of a vitamin A deficit. These studies showed that a depletion of vitamin A ester stores is caused by toxins, present in cigarette smoke (predominantly polyhalogenated compounds), in different tissues. 

Epstein-Barr virus early antigen induction. Methanol extract of the dried leaf, in cell culture at a concentration of 1 pg/mL, was inactive. The assay was designed for tumor-promoting activity . Two diastere-oisomers of 2,7,1 l-cembratriene-4,6-diol (a- and 3-CBT) from the neutral fractions of cigarette smoke condensate, in Raji cells, produced potent inhibitory effects on the induction of Epstein-Barr virus (EBV)-EA by 12-0-tetradecanoylphorbol-13-acetate (TPA). The doses of a- and P-CBT required for 50% inhibition of EBV-EA induction by TPA were 7.7 and 6.7 mg/mL, respectively. Application of a- and P-CBT to mouse skin before treatment with TPA, inhibited TPA-induced ornithine decarboxylase activity in a dose-dependent manner. Application of 16.5 pM/mouse of a- and p-CBT resulted... 

MAO inhibition. 2-Naphthylamine from smoke, in cell culture, inhibited mouse brain MAO A and B by mixed competitive-and noncompetitive-type inhibition . Mastocytoma induction. Cigarette smoke condensate suspensions ( tars ) from differ-... 

NT080 Villard, P. H., E. Seree, B. Lacarelle, et al. Effect of cigarette smoke on hepatic and pulmonary cytochromes P450 in mouse evidence for CYP2E1 induction in lung. Biochem Biophys Res Commun 1994 202(3) 1731-1737. 

NT169 Ohmori, T., H. Mori, and A. Riven-son. A study of tobacco carcinogenesis XX mastocytoma induction in mice by cigarette smoke particulates ( cigarette tar ). Am J Pathol 1981 102(3) 381-387. 

Van Cantfort, J., and J. Gielen. Organ specificity of aryl hydrocarbon hydroxylase induction by cigarette smoke in rats and mice. Biochem Pharmacol 1975 24 1253. 

The plasma clearance of theophylline varies widely. Theophylline is metabolized by the liver, so typical doses may lead to toxic concentrations of the drug in patients with liver disease. Conversely, clearance may be increased through the induction of hepatic enzymes by cigarette smoking or by changes in diet. In normal adults, the mean plasma clearance is 0.69 mL/kg/min. Children clear theophylline faster than adults (1-1.5 mL/kg/min). Neonates and young infants have the slowest clearance (see Chapter 59). Even when maintenance doses are altered to correct for the above factors, plasma concentrations vary widely. 

Finally, not only can drugs be substrates or inhibitors for CYP450 enzymes they can also be inducers. An inducer increases the activity of the enzyme over time because it induces the synthesis of more copies of the enzyme. One example of this is the effects of the anticonvulsant and mood stabilizer carbamazepine, which induces 3A4 over time (Fig. 6—19). Another example of CYP450 enzyme induction is cigarette smoking, which induces 1A2 over time (Fig. 6—20). The consequence of such enzyme induction is that substrates for the induced enzyme will be more efficiently metabolized over time, and thus their levels in the plasma will fall. Doses of such substrate drugs may therefore need to be increased over time to compensate for this. 

Chang, M.J., Walker, K., McDaniel, R.L. and Connell, C.T. (2005) Impaction collection and slurry sampling for the determination of arsenic, cadmium, and lead in sidestream cigarette smoke by inductively coupled plasma-mass spectrometry. Journal of Environmental Monitoring, 7(12), 1349-54. 

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