Polycyclic aromatic hydrocarbons metabolic activation

Thakker DR, Yagi H, Levin W, et al. Polycyclic aromatic hydrocarbons metabolic activation to ultimate carcinogens. In Anders MW, ed. Bioactivation of Foreign Compounds. Orlando, FL Academic Press 1985 177-242. 

D. R. Thakker, H. Yagi, W. Levin, A. W. Wood, A. H. Conney, D. M. Jerina, Polycyclic Aromatic Hydrocarbons Metabolic Activation to Ultimate Carcinogens , in Bioactivation of Foreign Compounds , Ed. M. W. Anders, Academic Press, Orlando, 1985, p. 177 - 242. 

HALL, M, and grover p l, (1990). Polycyclic aromatic hydrocarbons metabolism, activation, and tumor initiation , pp. 327-372. In c s cooper... 

The metabolic activity of other white-rot fungi including Phanerochaete chrysosporium and Pleurotus ostreacus has been discussed in the context of polycyclic aromatic hydrocarbons. For example, the mineralization potential of the manganese peroxide system fmmNematolomafrowardii for a number of substrates has been demonstrated (Hofrichter et al. 1998) the formation of CO2 from labeled substrates ranged from 7% (pyrene) to 36% (pentachlorophenol), 42% (2-amino-4, 6-dinitrotoluene), and 49% (catechol). 

Stereoselective Metabolism and Activations of Polycyclic Aromatic Hydrocarbons... 

Effects of Methyl and Fluorine Substitution on the Metabolic Activation and Tumorigenicity of Polycyclic Aromatic Hydrocarbons... 

Chemical carcinogenesis by polycyclic aromatic hydrocarbons (PAHs) is a multi-step process in which each of the steps must occur if a neoplasm is to develop. Thus, exposure to PAHs alone is not necessarily sufficient for the induction of a tumor. Many of these factors are summarized below and are discussed in various chapters of this volume. Considered here will be those factors influencing the reactions of the metabolically activated forms of the PAHs with DNA and the ways in which adducts may be detected and characterized. 

Covalent binding of chemical carcinogens to cellular macromolecules, DNA, RNA and protein, is wel1-accepted to be the first step in the tumor initiation process ( 1, 2). Most carcinogens, including polycyclic aromatic hydrocarbons (PAH), require metabolic activation to produce the ultimate electrophilic species which react with cellular macromolecules. Understanding the mechanisms of activation and the enzymes which catalyze them is critical to elucidating the tumor initiation process. 

Oxidation is intimately linked to the activation of polycyclic aromatic hydrocarbons (PAH) to carcinogens (1-3). Oxidation of PAH in animals and man is enzyme-catalyzed and is a response to the introduction of foreign compounds into the cellular environment. The most intensively studied enzyme of PAH oxidation is cytochrome P-450, which is a mixed-function oxidase that receives its electrons from NADPH via a one or two component electron transport chain (10. Some forms of this enzyme play a major role in systemic metabolism of PAH (4 ). However, there are numerous examples of carcinogens that require metabolic activation, including PAH, that induce cancer in tissues with low mixed-function oxidase activity ( 5). In order to comprehensively evaluate the metabolic activation of PAH, one must consider all cellular pathways for their oxidative activation. 

Karp, J.M., Rodrigo, K.A., Pei, P., Pavlick, M.D., Andersen, J.D., McTigue, D.J., Fields, H.W. and Mallery, S.R. (2005) Sanguinarine activates polycyclic aromatic hydrocarbon associated metabolic pathways in human oral keratinocytes and tissues. Toxicology Letters, 158, 50-60. 

In many mammals induction of monooxygenation by polycyclic aromatic hydrocarbons is accompanied by the formation of a hemoprotein not seen to any appreciable extent in non-induced animals. This leads to an alteration in the microsomal hemoprotein populations, a change in the metabolic activity of the microsomes and, hence, possible alterations in the toxicity of other chemicals (27, 8). 

S. K. Yang, M. Mushtaq, P. L. Chiu, Stereoselective Metabolism and Activation of Polycyclic Aromatic Hydrocarbons , in Polycyclic Hydrocarbons and Carcinogenesis , Ed. R. G. Harvey, American Chemical Society, Washington, 1985, p. 19 - 34. 

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