Polycyclic aromatic hydrocarbons enzyme induction

Conney, A.H. (1982). Induction of Microsomal-Enzymes by Foreign Chemicals and Carcinogenesis by Polycyclic Aromatic-Hydrocarbons—Clowes, G.H.A. Memorial Lecture. Cancer Research 42, 4875 917. 

The alteration of hemoprotein(s) P-450 subpopulations in the rat may be observed spectrally, because after treatment of rats with polycyclic aromatic hydrocarbons, the Soret maximum of the carbonmonoxyferrocytochrome complex undergoes a hypsochromic shift from 450 to 448nm (50). This blue shift was not seen with rainbow trout hepatic microsomes (29,30). However, this does not preclude the induction of novel hemoproteins P-450 since (a) the induced hemoprotein(s) maty not differ spectrally from the constitutive enzymes and (b) the induced-hemoprotein may account for only a small proportion of total hemoprotein P-450, and hence its contribution to the position of the Soret maximum of carbon monoxide-treated reduced microsomes may be negligible. The latter suggestion is supported by the work of Bend et al. with the little skate. These workers have shown that hepatic microsomes from 1, 2,3,4-dibenzanthracene treated skates did not exhibit a hypsochromic shift when compared to control microsomes, however, partially purified hemoprotein exhibited an absorbance maxima at 448 nm (51). 

Conney AH. Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons G. H. A. Clowes Memorial Lecture. Cancer Res 1982 42 4875-4917. 

The activity (induction or inhibition) of various CYP enzymes is influenced by a variety of factors that have been identified to date. For example, genetic polymorphisms are most significant in CYP families lA, 2A6, 2C9, 2C19, 2D6, and 2E1. Nutrition effects have been documented in families lAl, 1A2, IBl, 2A6,2B6, 2C8, 2C9, 2C19, 2D6, and 3A4 (10, 11) smoking influences families lAl, 1A2, and 2E1 (12) alcohol influences family 2E1 (13) drugs influence families lAl, 1A2, 2A6,2B6,2C, 2D6, 3A3, and 3A4,5 and environmental xe nobio tics such as polycyclic aromatic hydrocarbons. 

Cigarette smoke contains minute amounts of polycyclic aromatic hydrocarbons, such as benzol nr pyrene. which are potent inducers of microsomal cytochrome P-4S0 enzymes. This induction increases the oxidation of some drugs in nnokets. For example, theophylline is metabolized more rapidly in smokers than in nonsmokers. This difference is reflected in the marked difference in the plasma half-life of theophylline between smokers (r /2 4.1 hours) and non-smokers u A 7.2 hours). Other drugs, such as phenacetin. pentazocine. and propoxyphene, also reportedly undergo more rapid metabolism in smokers than in nonsmokers. " ... 

THE JOYS OF DISCOVERY ENZYME INDUCTION BY POLYCYCLIC AROMATIC HYDROCARBONS... 

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