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Chemical fractions of a model diesel exhaust particulate extract, notably the fraction containing polycyclic aromatic hydrocarbons (PAH) (Fraction II), mono-nitro PAH (Fraction III), and dinitro-PAH (Fraction IV) have been shown to displace binding of 2,3,7,8-tetrachloro[1,6-[3H]]dibenzo-p-dioxin (TCDD) from the rat liver cytosol aryl hydrocarbon (Ah) receptor. The Ah receptor binding activity of twenty-seven PAH, identified in Fraction II and recombined in the same proportions as those observed in the original fraction, was not significantly different to that of Fraction II, suggesting that the binding activity of this, fraction can be explained by the identified components. In addition, these two samples had the ability to induce expression of an Ah receptor target gene, CYP450lA1, as indicated by solution hybridisation assay of mRNA levels in mouse Hepa 1c1c7 cells. On screening of the individual reference PAH, the following compounds displayed IC50 values for the Ah receptor binding < l μM: benzo(a)-fluorene, benz(a)anthracene, chrysene, benzo(b)fluoranthene, benzo(a)pyrene and indeno(1,2,3-cd)pyrene. These six compounds also induced the expression of CYP4501A1 in the range 2–6-fold above baseline levels. Further studies demonstrated that the Ah receptor binding activity of Fraction II could be explained by the presence of these six PAR The chromatographic behaviour and Ah receptor binding affinity of reference mono-nitro PAH, indicate that 3-nitroperylene, 6-nitrobenzo(a)pyrene and 7-nitrobenz(a)-anthracene are candidate compounds responsible for the high Ah binding activity observed in Fraction III. |
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