Carcinogenic effects of PAHs

As discussed in Sections 2.3.5 and 2.4, it is currently believed that the toxic and carcinogenic effects of PAHs are mediated by reactive diol-epoxide intermediates that interact directly with DNA and RNA, producing adducts. The formation of these adducts leads to neoplastic transformation as well as interfering with the normal functioning of rapidly proliferating tissues. As discussed above, these reactive intermediates are formed when PAHs are biotransformed by the P-450 enzymes. Interference with these metabolic pathways, by inactivation of the activated diol epoxides, reduction in tissue levels of cytochrome P-450, and direct inhibition of the cytochrome P-450 enzymes responsible for the formation of the reactive intermediates, could reduce the toxic and carcinogenic effects of PAHs. A number of drugs, such as cobaltous chloride, SKF-525-A, and 6-nitro-... 

The potential mutagenic and carcinogenic effects of PAHs are the basic reasons of concern for the levels of these compounds in the environment. The first cancers to be associated with PAH-containing substances were through skin contact that resulted in scrotal cancer of chimney sweeps and skin cancer among mule spinners in the cotton, wool, and jute industries. 

PAH bind to the Ah receptor, this effect is not the only effect that determines the carcinogenic potency of PAH. DNA binding and induction of mutations are other significant effects in the carcinogenesis of PAH, and there is no indication that different PAH are activated via the same metabolic route, binds DNA in the same positions, and induce the same types of mutations in the same organs or tissues. In fact, the study by Culp et al. (1998) showed that a coal-tar mixture of PAH also produced tumors in other tissues and organs than those affected by benzo[a]pyrene alone, and that the additional PAH in the mixture did not significantly contribute to the incidence of stomach tumors observed after benz[a]pyrene alone. 

Carcinogenic effects of environmental mixtures on children are not limited to in utero exposures. In a study conducted on children who resided in two of the most polluted cities in the Silesia province of Poland, it was found that simultaneous exposure to PAHs and lead (emissions from coalburning stoves) led to the induction of cytogenic effects in peripheral lymphocytes. I11 A study in Great Britain found that childhood cancers are strongly elevated by both prenatal and early postnatal exposures to oil-based combustion gases, particularly from engine exhausts. 121... 

The workers were also exposed to asbestos, radiation, and other unspecified chemicals. Positive associations were observed between the exposures and rates of death from lung, lymphopoietic, bladder, and kidney cancers. Kerosene fuels, which contain PAHs and asbestos, are associated with lung cancer, but not with the other cancers. Methyl hydrazine is not a known human carcinogen. Similar results were reported for the carcinogenic effects of lipophilic PAHs in combination with hydrophilic chemicals for aluminum workers, coal gasification workers, and chimney sweeps. I17 ... 

A method for assessing the potential carcinogenic effects of these PAHs would be to use the EPA cancer risk levels for benzo(a)pyrene and the relative potency factors for the individual PAHs (Table 6-7). 

Dermal Effects. Mixtures of carcinogenic PAHs cause skin disorders in human and animals however, specific effects in humans of individual PAHs. except for benzo[a]pyrene. have not been reported. Mixtures of PAHs are also used to treat some skin disorders in humans. From these patients comes much ofthe data describing dermal effects of PAH exposure. 

Delistraty, D. 1998. A critical revew of the application of toxic equivalency factors to carcinogenic effects of polycyclic aromatic hydrocarbons in mammals pp. 312-359. In PAHs and Related Compounds, Vol. 3.J (A.H. Neilson ed.) Springer-Verlag, Berlin. 

One of the most significant and harmful effects of PAHs is due to their carcinogenic nature, although this is not consistent across the whole range of compounds. Eight of the four, five and six membered ring PAHs are considered to be carcinogens. 

The carcinogenic effects of these fractions are presented in figure 3 which clearly shows that almost the full activity remains in the small fraction containing 4-7 ring PAH, which is only 3.5% by weight of the total condensate Moreover, this fraction follows the same dose-response relation as the crude condensate (fig 4),... 

Most of the studies on the health effect of PAHs have been carried out on laboratory animals than on humans due to the ethical implications. Therefore there exist practically no published studies on health effects in human following oral exposure to PAHs. In most cases humans are occasionally exposed to a mixture of PAHs through inhalation and dermal exposure. Other drawback associated with these data is that all the reports on human exposure to PAHs have the same subjects exposed to other potentially carcinogenic chemicals in occupational and environmental situations. Information on health effect of these mixtures is thus confined to their carcinogenic potentials derived from a number of epidemiological studies. 

Polycyclic aromatic hydrocarbons (PAH) in atmospheric particles have received a great deal of attention because of the known carcinogenic effects of some of these compounds. The most prominent of these compounds is benzo(a)pyrene and other examples are benz(a)anthracene, chrysene, benzo(e)pyrene, benz(e)acephenanthrylene, benzo(j)fluoranthene, and indenol. Some representative structures of PAH compounds are given as follows ... 

Polycyclic aromatic hydrocarbons are potent immunosuppressive environmental contaminants. Immunotoxic effects of PAHs, which may contribute to their carcinogenic potential, have been established in various animal models and in human immune cells (van Grevenynghe et al., 2004). Inhibition of the production of immunocompetent cells (lymphocytes and monocytes) is likely one of the mechanisms contributing to the immunosuppression due to PAHs. Exposure to PAHs inhibits the differentiation of monocytes into dendritic cells and macrophages it also induces apoptosis of both pre-T cells in the thymus and pre-B cells in the bone marrow, which may account for thymic atrophy and decreased lymphoid cell recovery from the spleen, lymph nodes, and bone marrow in PAH-exposed mice (Lutz et al., 1998 Page et al., 2002). These toxic effects towards precursors of immune cells have been linked, at least in part, to the PAHs metabolism into toxic reactive intermediates triggering apoptosis of pre-B eells (Mann et al., 1999). 

Carcinogenic Assessment of Pahs Toxic Effect of Pahs... 

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