Carcinogenicity of polycyclic aromatic hydrocarbons

JECFA (2005) used this approach to evaluate the carcinogenicity of polycyclic aromatic hydrocarbons (PAH), acrylamide, and ethyl carbamate in food. 

Norden, B., Edlund, U., and Wold, S., Carcinogenicity of polycyclic aromatic hydrocarbons, studied by SIMCA pattern recognition, Acta Chemica Scandinavica Series B, 32, 602-608, 1978. 

The Pullmans were the first to use electronic structure calculations in several studies on the carcinogenicity of polycyclic aromatic hydrocarbons and hetero analogs in the late 1940s and early 1950s. Much of the early work on... 

G. Klopman, K. Namboodiri, and A. N. Kalos, in Molecular Basis of Cancer, Part A Macromolecular Structure, Carcinogens and Oncogenes, R. Rein, Ed., Alan R. Liss, 1985, pp. 287—298. Computer Automated Evaluation and Prediction of the Iball Index of Carcinogenicity of Polycyclic Aromatic Hydrocarbons. 

Villemin, D., Cherqaoui, D. and Mesbah, A. (1994). Predicting Carcinogenicity of Polycyclic Aromatic Hydrocarbons from Backpropagation Neural Network. J.Chem.lnf.Comput.Sci., 34, 1288-1293. 

Ville.min D, Cherqaoui D, Mesbah A. Predicting carcinogenicity of polycyclic aromatic hydrocarbons from back-propagation neural network. J Chem Inf Comput Sci 1994 34 1288-93. 

Straif, K., Baan, R., Grosse, Y., Secretan, B., El Ghissassi, E., and Cogliano, V. (2005). Carcinogenicity of polycyclic aromatic hydrocarbons. Lancet Oncol 6, 931-932. 

A large number of polycyclic aromatic hydrocarbons are known Many have been synthesized m the laboratory and several of the others are products of com bustion Benzo[a]pyrene for example is present m tobacco smoke contaminates food cooked on barbecue grills and collects m the soot of chimneys Benzo[a]pyrene is a carcinogen (a cancer causing substance) It is converted m the liver to an epoxy diol that can induce mutations leading to the uncontrolled growth of certain cells... 

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. 

The NO + 03 chemiluminescent reaction [Reactions (1-3)] is utilized in two commercially available GC detectors, the TEA detector, manufactured by Thermal Electric Corporation (Saddle Brook, NJ), and two nitrogen-selective detectors, manufactured by Thermal Electric Corporation and Antek Instruments, respectively. The TEA detector provides a highly sensitive and selective means of analyzing samples for A-nitrosamines, many of which are known carcinogens. These compounds can be found in such diverse matrices as foods, cosmetics, tobacco products, and environmental samples of soil and water. The TEA detector can also be used to quantify nitroaromatics. This class of compounds includes many explosives and various reactive intermediates used in the chemical industry [121]. Several nitroaromatics are known carcinogens, and are found as environmental contaminants. They have been repeatedly identified in organic aerosol particles, formed from the reaction of polycyclic aromatic hydrocarbons with atmospheric nitric acid at the particle surface [122-124], The TEA detector is extremely selective, which aids analyses in complex matrices, but also severely limits the number of potential applications for the detector [125-127],... 

Grimmer, G., H. Brune, R. Deutsch-Wenzel, G. Dettbam, J. Misfeld, U. Able, and J. Timm. 1985. The contribution of polycyclic aromatic hydrocarbon fractions with different boiling ranges to the carcinogenic impact of emission condensate from coal fired residential furnaces as evaluated by topical application to the skin of mice. Cancer Lett. 28 203-211. 

Neff, J.M. 1982a. Accumulation and release of polycyclic aromatic hydrocarbons from water, food, and sediment by marine animals. Pages 282-320 in N.L. Richards and B.L. Jackson (eds.). Symposium Carcinogenic Polynuclear Aromatic Hydrocarbons in the Marine Environment. U.S. Environ. Protection Agency Rep. 600/9-82-013. 

CYP1A1. In humans, of the two members, CYP1A2 is the major player while CYP1A1 is a relatively minor extrahepatic isoform associated with the oxidation of polycyclic aromatic hydrocarbons like benzo[a]pyrene. Similarly, in test rodent species it is responsible for the generation of toxic intermediates and carcinogenic metabolites (10). 

Grimmer G et al Quantification of the carcinogenic effects of polycyclic aromatic hydrocarbons in used engine oil by topical application onto the skin of mice. Int Arch Occup Environ Health 50 95-100, 1982... 

Grimmer G et al Characterization of polycyclic aromatic hydrocarbons as essential carcinogenic constituents of coal combustion and automobile exhaust using mouse-skin-painting as a carcinogen-specific detector. Toxicol Environ Chem 6 97, 1983... 

In 1775, Pursevil Pott first noted that the compounds associated with soot caused scrotal cancer in British chimney sweeps (] ). Not having modern methods of Instrumental analysis available to him, Pott was unable to specify the chemical structures of these compounds. It remained until 1933 before Cook et al. identified the exact structure of benzo[a]pyrene and demonstrated its carcinogenicity ( ). Thus, polycyclic aromatic hydrocarbons (PAH) are one of the few groups of compounds which are known to be carcinogenic to man. 

K. -W. Naujack, U. Mohr, and H. Ernst, Contribution of Polycyclic Aromatic Hydrocarbons and Nitro-Derivatives to the Carcinogenic Impact of Diesel Engine Exhaust Condensate Evaluated by Implantation into the Lungs of Rats, Cancer Lett., 37, 173-180 0 987). 

Oxidation to Arene Oxides and Arene Diols. Arene oxides and arene diols have been widely studied particularly concerning the metabolism of polycyclic aromatic compounds and their implication as intermediates responsible for the carcinogenicity and mutagenicity of polycyclic aromatic hydrocarbons.803,804... 

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