Carcinogenic Activity of Polycyclic Aromatic Hydrocarbons

Classifying the Carcinogenic Activity of Polycyclic Aromatic Hydrocarbons 

The best prediction statistics for each kernel type are presented here linear, ACp = 0.76 polynomial, degree 2, ACp = 0.82 RBF, y = 0.5, ACp = 0.86 neural, a = 2, b = 0, ACp = 0.66 and anova, y = 0.5, d = 1, ACp = 0.84 (C = 10 for these SVM models). The relationship between the quantum indices and PAH carcinogenicity is nonlinear, as evidenced by the increase in prediction power when going from a linear to an RBF kernel. 

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Vendrame, R., Braga, R.S., Takahata, Y. and Galvao, D.S. (1999). Structure-Activity Relationship Studies of Carcinogenic Activity of Polycyclic Aromatic Hydrocarbons Using Molecular Descriptors with Principal Component Analysis and Neural Network Methods. J.Chem.lnf. Comput.Sci.,39,1094-1104. 

Barone, P.M.V.B., Braga, R.S., Camilo, A., Jr and Galvao, D.S. (2000) Electronic indices from semi-empirical calculations to identify carcinogenic activity of polycyclic aromatic hydrocarbons. J. Mol. Struct. (Theochem), 505, 55-66. 

Coluci, V.R., Vendrame, R., Braga, R.S. and Gamper, A.M. (2002) Identifying relevant molecular descriptors related to carcinogenic activity of polycyclic aromatic hydrocarbons (PAHs) using pattern recognition methods./. Chem. Inf. Comput. Sci., 42. 1479-1489. 

D.D. Morgan, D. Warshawsky, T. Atkinson (1977). The relationship between carcinogenic activities of polycyclic aromatic hydrocarbons and their singlet, triplet, and singlet-triplet splitting energies and phosphorescence lifetimes. Photochem. Photo-bioL, 25, 31-38. 

Molecular structure and carcinogenic activity of polycyclic aromatic hydrocarbons... 

It is well-known that some polycyclic aromatic hydrocarbons, such as benzo(a)pyrene, are strong carcinogens, while some other polycyclic aromatic hydrocarbons with quite similar molecular structure, such as benzo(a)naphthacene, having no carcinogenic activity. In order to find the regularities of the carcinogenic activity of polycyclic aromatic hydrocarbons, quantum chemical parameters and molecular descriptors have been used for SVM computation. 

THEOCHEM), 505, 55-66 (2000). Electronic Indices from Semi-empirical Calculations to Identify Carcinogenic Activity of 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. 

The reason that one-electron oxidation is suggested as playing a central role in the metabolic activation of polycyclic aromatic hydrocarbons derives from certain features of the radical cations that are common to the most potent carcinogens of the family ... 

Activation of polycyclic aromatic hydrocarbon trans-diliydrodiol proximate carcinogens by human aldo-keto reductase (AKR1C) enzymes and their functional overexpression in human lung adenocarcinoma (A549) cells. J. Biol. Chem., 277, 24799-24808. 

Luch, A. and Baird, W.M. (2005) Metabolic activation and detoxification of polycyclic aromatic hydrocarbons, in The Carcinogenic Effects of Polycyclic Aromatic Hydrocarbons (ed. A. Luch), Imperial College Press, London,... 

Epoxide Hydrolase. Epoxide hydrolase (EH) activity has been studied in numerous tissues with many different substrates (71-72). Hepatic microsomal EH has been shown to be induced by polycyclic aromatic hydrocarbons, but is insensitive to cytochrome P-450 type inducers (73). Epoxide hydrolase has been related to the activation of polycyclic aromatic hydrocarbons into reactive carcinogens (70). Epoxide hydrolase activity has been determined... 

Santodonato, J. 1997. Review of the estrogenic and antiestrogenic activity of polycyclic aromatic hydrocarbons relationship to carcinogenicity. Chemosphere, v.34, p.835-848. 

Methods for the synthesis of the biologically active dihydrodiol and diol epoxide metabolites of both carcinogenic and noncarcinogenic polycyclic aromatic hydrocarbons are reviewed. Four general synthetic routes to the trans-dihydrodiol precursors of the bay region anti and syn diol epoxide derivatives have been developed. Syntheses of the oxidized metabolites of the following hydrocarbons via these methods are described benzo(a)pyrene, benz(a)anthracene, benzo-(e)pyrene, dibenz(a,h)anthracene, triphenylene, phen-anthrene, anthracene, chrysene, benzo(c)phenanthrene, dibenzo(a,i)pyrene, dibenzo(a,h)pyrene, 7-methyl-benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, 3-methylcholanthrene, 5-methylchrysene, fluoranthene, benzo(b)fluoranthene, benzo(j)fluoranthene, benzo(k)-fluoranthene, and dibenzo(a,e)fluoranthene. 

An early theory linking the structure of polycyclic aromatic hydrocarbons with carcinogenesis is the K-region theory of Pullman and Pullman,197,198 according to which (1) carcinogenic activity in aromatic hydrocarbons is determined by the existence of an active K-region, and (2) if the molecule... 

Exposure of cells to carcinogens may result in the formation of DNA adducts varying in size from methyl groups to bulky structures, such as metabolites of polycyclic aromatic hydrocarbons and aromatic amines. In vivo, these adducts usually are removed enzymatically and at different rates from the DNA. Because the liver is the main site of activation of chemical carcinogens, the DNA of this organ usually forms more adducts. Direct detection and measurement of DNA damage are thus possible, in principle, by detection and measurement of the bound adduct. Because the number of adducts is usually extremely small, very sensitive methods cure required for their measurement. 

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