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Polycyclic Aromatic Hydrocarbons (PAHs): The Role of Human Transport Systems in the Fate and Toxic Effects

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Polycyclic Aromatic Hydrocarbons (PAHs): The Role of Human Transport Systems in the Fate and Toxic Effects
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Abstract

<p>Presented are the results of the analysis of the published data on the interaction of Polycyclic Aromatic Hydrocarbons (PAHs), known carcinogenic compounds, and their toxic metabolites, with human transporters. The results of the study show that¸ the compounds interact with human transporters as substrates (with 44% of the data), as inducers (with 24% of the data), and as inhibitors (with 32% of the data). PAH compounds metabolites are preferentially transported in the form of the highly polar glucuronides (Glu-conjugates), potentially toxic sulfate-conjugates (Sul-conjugates), and glutathione conjugates (mercapturic acids). Glucuronides and sulfate-conjugates are formed in reactions with OH-groups of the PAH metabolites, and glutathione conjugates react with the toxic epoxide metabolites, being excreted as mecapturic acids. The analysis of the published literature also shows major participation of hOAT transporters (33% of the reactions), MDR1 (P-gp), participate with 21%, and MRP transporters with 18%. The results obtained for the example PAHs and the metabolites are discussed, referring to their application, distribution, excretion, and toxicity to humans. The results also indicate that more research is needed on the transporters' role in the toxicity and fate of PAHs and metabolites in humans.<br></p>

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