Polycyclic aromatic hydrocarbons implications

Polycyclic Aromatic Hydrocarbons Implications for Developmental, Molecular, and Behavioral Neurotoxicity... 

POLYCYCLIC AROMATIC HYDROCARBONS IMPLICATIONS FOR DEVELOPMENTAL, MOLECULAR, AND BEHAVIORAL NEUROTOXICITY... 

Epoxides are often encountered in nature, both as intermediates in key biosynthetic pathways and as secondary metabolites. The selective epoxidation of squa-lene, resulting in 2,3-squalene oxide, for example, is the prelude to the remarkable olefin oligomerization cascade that creates the steroid nucleus [7]. Tetrahydrodiols, the ultimate products of metabolism of polycyclic aromatic hydrocarbons, bind to the nucleic acids of mammalian cells and are implicated in carcinogenesis [8], In organic synthesis, epoxides are invaluable building blocks for introduction of diverse functionality into the hydrocarbon backbone in a 1,2-fashion. It is therefore not surprising that chemistry of epoxides has received much attention [9]. 

Man has served as the unintentional guinea pig for the identification of some major classes of carcinogens. These include the polycyclic aromatic hydrocarbons (PAH), or polyarenes, which have been identified as the active components of soot, which was recognized by the London surgeon Percivall Pott two centuries ago as responsible for cancer of the scrotum in chimney sweeps. Subsequently, polycyclic hydrocarbons have been implicated as agents responsible for skin cancer in other occupations such as shale oil distillation and mule spinning in the cotton industry. 

It is sometimes assumed that every phenol metabolite indicates the formation of an arene oxide intermediate however, as discussed above, arene oxides are not obligate intermediates in the formation of phenols. This is an important distinction because arene oxides and other epoxides are reactive intermediates that can be toxic or even carcinogenic, e.g., epoxides of some polycyclic aromatic hydrocarbons. The question of whether their formation is obligatory is significant for drug design and development and has implications for toxicity as discussed in Chapter 8. 

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... 

Polycyclic Aromatic Hydrocarbons Exposure from Emission Products and from Terrorist Attacks on US Targets - Implications for Developmental Central Nervous System Toxicity... 

Occurrence and transport of HCs have important implications for health of biota as well as humans. Of the top 20 contaminants on the USEPA Hazardous Substances Priority List, 15 are hydrophobic (USEPA, 1999). These contaminants include trace elements, organochlorine compounds, and polycyclic aromatic hydrocarbons (PAHs). A major fraction of HCs are transported adhered to suspended sediment (Bradford and Horowitz, 1982 Garbarino et al., 1995 Rostad et al., 1995). 

Cziczo DJ, Thomson DS, Murphy DM (2001) Ablation, flux, and atmospheric implications of meteors inferred from stratospheric aerosol. Science 291 1772-1775 Dachs J, Eisemeich SJ (2000) Adsorption onto aerosol soot carbon dominates gas-particle partitioning of polycyclic aromatic hydrocarbons. Environ Sci Technol 34 3690-3697 Dalleska NF, Colussi AJ, Hyldahl AM, Hoffmaim MR (2000) Rates and mechanism of carbonyl sulfide oxidation by peroxides in concentrated sulfuric acid. J Phys Chem A 104 10794-10796 D Almeida GA, Schitz L (1983) Number, mass, and volume distributions of mineral aerosol and soils of the Sahara. J Clim Appl Meteorol 22 233-243... 

Complex chemical mixtures in coke oven emissions is known to result in DNA adduct formation. Free oxygen radicals and CYP450 are implicated in the pathogenesis. Polycyclic aromatic hydrocarbons, which are primary compounds in coke oven emissions generated by the coking process, cause cancer and mutagenesis by a multitude of mechanisms including DNA adduct formation and metabolism. 

Weston, D.P. and Mayer, L.M. (1998a) In vitro digestive fluid extraction as a measure of the bioavailability of sediment-associated polycyclic aromatic hydrocarbons sources of variation and implications for partitioning models. Environ. Toxicol. Chem., 17, 820-829. 

Gowlan, B.T., McIntosh, A.D., Davies, I.M., Moffat, C.F. and Webster, L. (2002) Implications from a field study regarding the relationship between polycyclic aromatic hydrocarbons and glutathione S-transferase activity in mussels. Mar. Environ. Res., 54, 231-235. 

Woods, P.E., J.D. Paulauskis, L.A. Weight, M.A. Romano, and S.I. Guttman. 1989. Genetic variation in laboratory and field populations of the midge, Chironomus tentans Fab. Implications for toxicology. Environ. Toxicol. Chem. 8 1067-1074. Yunker, M.B. and R.W. Macdonald. 1995. Composition and origins of polycyclic aromatic hydrocarbons in the Mackenzie River and on the Beaufort Sea Shelf. Arctic 48 118-129. 

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... 

PET is the key feature of many other photo-oxidations involving aromatic substrates. It has been shown, for example, that pyrene and anthracene which are covalently attached to silica, gold or indium-doped tin oxide (ITO), undergo a photo-oxidation forming dihydroxy/dione derivatives. The reaction involves 02, formed by ET between excited pyrene, or anthracene, and O2, and it is suggested that the implications of such a photodegradation need to be considered when polycyclic aromatic hydrocarbons (PAHs) are used as spectroscopic probes in surface adlayers. The redox photosensitized amination of 1,2-benzo-1,3-cycloalkadienes, arylcyclopropanes, and quadricyclane with ammonia and primary amines, using 1,2,4-triphenylbenzene (1,2,4-TPB) or 2,2 -methylenedioxy-1,1 -binaphthalene in the presence of m- or p-dicyano-benzene (DCB), has been described (Scheme 51). The process involves the formation of the radical cation of 1,2,4-TPB, for example, by PET to the DCB, followed by hole transfer from the radical cation to the substrate, the latter... 

Kaupp H, McLachlan MS (1998) Atmospheric particle size distributions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polycyclic aromatic hydrocarbons (PAHs) and their implications for wet and dry deposition. Atmos Environ 33 85-95 Kaupp H, McLachlan MS (1999) Gas/particle partitioning of PCDD/Fs, PCBs, PCNs and PAHs. 

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