Antagonistic and synergistic interactions during the binding of binary mixtures of polycyclic aromatic hydrocarbons to the aryl hydrocarbon receptor

• Published in: Toxicology in vitro 2018-08, Vol.50, p.54-61
• Main Authors: Pushparajah, Daphnee S., Ioannides, Costas
• Format: Article
• Language: English
• Subjects: Anthracene; Aromatic compounds; Aryl hydrocarbon receptor; Avidity; Benzo(a)pyrene; Binary mixtures; Binding; Binding sites; Carcinogenesis; Carcinogenicity; Carcinogens; Chrysene; Cytochrome P450; Interactions; Liver; Molecules; Organic chemistry; Polycyclic aromatic hydrocarbons; Precision-cut tissue slices; Pyrene; Rodents; Synergism
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2018.02.011

In order to assess the potential of polycyclic aromatic hydrocarbons (PAHs) to interact with each other, benzo(a)pyrene (B(a)P) was incubated either alone or in combination with other isomeric 5-ring PAHs in precision-cut rat liver slices. At the end of the incubation, the slices were removed and the O-deethylation of ethoxyresorufin (EROD) was determined in microsomal preparations. The BP-mediated rise in EROD activity was suppressed in the presence of dibenzo(a,j)anthracene, dibenzo(a,c)anthracene and picene, whereas it was increased in the presence of pentacene. In the case of benzo(b)chrysene, benzo(c)chrysene and benzo(g)chrysene the effect was concentration-dependent with both antagonism and synergism being observed. The binding of B(a)P to the aryl hydrocarbon (Ah) receptor was similarly modulated by other PAHs. No correlation was evident between binding avidity of the PAH to the Ah receptor and either its potential for interaction or nature of interaction, e.g. synergism or antagonism. These interactions were also independent of the molecular shape (ring arrangement) of the 5-ring isomeric PAHs. Bearing in mind the role of the Ah receptor in chemical carcinogenesis, it may be concluded that interactions at the Ah receptor site may contribute to the well-established modulation of the carcinogenicity of one PAH in the presence of another. •Benzo[a]pyrene [BP]-induced EROD activity in liver is modulated by other PAHs.•The binding of BP to the AhR is modulated by the presence of other PAHs.•Interactions between BP and other PAHs can be synergistic or antagonistic in nature.•Modulation of BP binding to the AhR by PAHs is independent of their shape.•Modulation of BP binding by other PAHs is not related to their affinity for the AhR.