title: Effects of carcinogenic versus non-carcinogenic AHR-active PAHs and their mixtures: lessons from ecological relevance.
abstract: Polycyclic aromatic hydrocarbons (PAHs) are priority environmental mutagens and carcinogens that occur in the aquatic environment as mixtures rather than the individual compounds for which guidelines are issued. The present work aimed at understanding the interaction effects between carcinogenic and non-carcinogenic PAHs in a model marine fish (Dicentrarchus labrax) in realistic scenarios. Laboratory assays under ecologically-relevant parameters were conducted for 28 days with sediments spiked with low-moderate concentrations (250-800ngg(-1)) of two model PAHs, phenanthrene (non-carcinogenic) and benzo[b]fluoranthene (carcinogenic to experimental animals). Both PAHs induced hepatic histopathological changes that indicate metabolic failure and inflammation, especially in animals exposed to mixtures. Phenanthrene elicited biochemical changes better related to oxidative stress (lipid peroxidation, glutathione and glutathione S-transferase activity) and CYP function, whereas B[b]F disrupted metabolic responses and defences to toxicological challenge. Conversely, mixed PAHs yielded lesions and responses that, altogether, are compatible with the AHR dependent pathway (the basis of PAH mutagenicity), potentially generating supra-additive effects. Nonetheless, the low, ecologically-relevant, concentrations of PAHs diluted dose and time-response relations. Overall, although seemingly predicting the risk of individual PAHs, environmental guidelines may not apply to mixtures by underestimating adverse effects, which calls for a redefinition of standards when determining the true risk of toxicants under realistic circumstances.
authors.affiliation: MARE - Marine and Environmental Sciences Centre, Departamento de Ciências e Engenharia do Ambiente, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, Portugal; IPMA-Instituto Português do Mar e da Atmosfera, Avenida do Brasil, 1449-006 Lisboa, Portugal. Electronic address: marta.martins@fct.unl.pt.
authors.forename: Marta
authors.initials: M
authors.lastname: Martins
authors.affiliation: MARE - Marine and Environmental Sciences Centre, Departamento de Ciências e Engenharia do Ambiente, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: José M
authors.initials: JM
authors.lastname: Santos
authors.affiliation: UCIBIO-Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal.
authors.forename: Mário S
authors.initials: MS
authors.lastname: Diniz
authors.affiliation: IPMA-Instituto Português do Mar e da Atmosfera, Avenida do Brasil, 1449-006 Lisboa, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ferreira
authors.affiliation: MARE - Marine and Environmental Sciences Centre, Departamento de Ciências e Engenharia do Ambiente, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Maria H
authors.initials: MH
authors.lastname: Costa
authors.affiliation: MARE - Marine and Environmental Sciences Centre, Departamento de Ciências e Engenharia do Ambiente, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Costa
mesh_terms: D000818:Animals; D001492:Bass / Q000378:metabolism*; D002273:Carcinogens / Q000633:toxicity*; D005449:Fluorenes / Q000633:toxicity*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010616:Phenanthrenes / Q000633:toxicity*; D011897:Random Allocation; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D005449:Fluorenes; D010616:Phenanthrenes; D014874:Water Pollutants, Chemical; C031181:phenanthrene; D006899:Mixed Function Oxygenases
keywords: Aryl hydrocarbon receptor; Benzo[b]fluoranthene; Histopathology; Oxidative stress; Phenanthrene