Mixed function oxidases polycyclic aromatic hydrocarbons

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. 

Aryl hydrocarbon hydroxylase (AHH) is a complex mixed function oxidase enzyme which converts polycyclic aromatic hydrocarbons such as DMBA to more hydrophilic and readily excretable products. During this process metabolites that are more carcinogenic than the parent compound can be produced. The distribution of MFO enzymes, their activity, and the balance between conversion of procarcinogens to active carcinogens and their detoxification is probably a... 

Aryl hydrocarbon hydroxylase (AHH) is part of the microsomal mixed-function oxidase system involved in the detoxification of polycyclic aromatic hydrocarbons. In the HPLC assay developed for the AHH activity, benzo[a]pyrene (BaP) is used as the substrate, and the activity is determined by measuring the unreacted BaP during the reaction. 

James, M.O. and J.R. Bend. Polycyclic aromatic hydrocarbon induction of cytochrome P-450-dependent mixed-function oxidases in marine fish. Toxicol. Appl. Pharmacol. 54 117—133, 1980. 

The polycyclic aromatic hydrocarbons (PAH) are common environmental pollutants that have been implicated as etiological factors in human chemical carcinogenesis (13, 14). One such PAH that has been studied extensively is benzo[a]-pyrene (G3). The metabolic activation of this compound to various reactive intermediates, including epoxides, phenols, and quinones, is performed by the cytochrome-P450-containing mixed function oxidase (MFO) system. Subsequent metabolic steps may involve the hydration of epoxides to dihydrodiols, mediated... 

The polycyclic aromatic hydrocarbon carcinogens, which are very ubiquitous, are metabolized by the microsomal mixed-function oxidase system of target tissues to a variety of metabolites such as phenols, quinones, epoxides, dihydrodiols and dihydrodiol-epoxides ( ). The mqjor pathway of activation of benzo(a)pyrene (BP) leads to the formation of dihydrodiol-epoxide of BP which interacts predominantly with the 2-amino of guanine of DNA. The dihydrodiol-epoxide of BP appears to be the major ultimate electrophilic, mutagenic, and carcinogenic metabolite of BP ( ). Nevertheless, other metabolites such as certain phenols, epoxides and quinones may contribute to the overall carcinogenic activity of BP. In addition, a free radical mechanism may also be partly involved in its carcinogenic activity. 

Batel R, Bihari N, Kurelec B, Muller WEG, Zahn RK (1983) Presence of mixed function oxygenases in some marine invertebrates. Thalassia Jugoslav 19 23-29 Batel R, Bihari N, Zahn RK (1986) Purification and characterization of a single form of cytochrome P-450 from the spiny crab Maja crispata. Comp Biochem Physiol 83C 165-170 Batel R, Bihari N, Zahn RK (1988) 3-methylcholanthrene does induce mixed function oxidase activity in hepatopancreas of spiny crab Maja crispata. Comp Biochem Physiol 90C 435-438 Bauer JE, Kerr RP, Bautista MF, Decker C J, Capone DG (1988) Stimulation of microbial activities and polycyclic aromatic hydrocarbon degradation in marine sediments inhabited by Capitella capitata. Mar Env Res 25 63-84... 

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