Interaction of Polycyclic Aromatic Hydrocarbon Compounds in Fish Primary Hepatocytes: From Molecular Mechanisms to Genotoxic Effects

32 Pages Posted: 30 Jun 2022

See all articles by Marta Martins

Marta Martins

affiliation not provided to SSRN

Isabella Bramatti

affiliation not provided to SSRN

Beatriz Matos

affiliation not provided to SSRN

Neusa Figueiredo

affiliation not provided to SSRN

Pedro Pousão-Ferreira

affiliation not provided to SSRN

Vasco Branco

affiliation not provided to SSRN

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants normally found in the environment as complex mixtures. Single PAHs are classified as mutagenic and carcinogenic pollutants, but the interaction effects between them may trigger different toxicological mechanisms and, consequently, yield different effects to organisms. The present work addresses the interaction effects of three PAHs with different carcinogenic potential and chemical structure, in primary liver cells of gilt-headed seabreams ( Sparus aurata ). After cell exposure to Phenanthrene (Phe), Benzo[a]pyrene (B[a]P) and Benzo[b]fluoranthene (B[b]F) and their mixtures several cell responses were analysed: cellular viability, CYP1A1 activity by the EROD assay, CYP1A1 protein levels by Western blot; transcript (mRNA) levels of CYP1A1, EPX and GST (qRT-PCR); genotoxic effects by the Comet assay. Results show that B[a]P induces CYP1A1 gene and protein expression increasing its activity and, therefore, increasing the production of metabolites that trigger genotoxic DNA damage. In mixtures containing Phe and B[a]P increased in CYP1A1 mRNA levels and DNA damage (up to 70%) which suggests that, although Phe is considered a non-carcinogenic PAH, it potentiates CYP1A1 synthesis induced by B[a]P, increasing DNA strand breakage. Overall, the findings indicate that the upregulation of CYP1A1 by carcinogenic PAH will not weaken even when in mixtures with non-carcinogenic PAH. In fact, PAHs mixtures containing non-carcinogenic PAH may potentiate the genotoxic effect of carcinogenic PAH. Our results highlight the need for a redefinition of the environmental risk assessment strategy for mixtures of carcinogenic pollutants.

Keywords: CYP1A, DNA strand breakage, Phenanthrene, Benzo[a]pyrene, Benzo[b]fluoranthene.

Suggested Citation

Martins, Marta and Bramatti, Isabella and Matos, Beatriz and Figueiredo, Neusa and Pousão-Ferreira, Pedro and Branco, Vasco, Interaction of Polycyclic Aromatic Hydrocarbon Compounds in Fish Primary Hepatocytes: From Molecular Mechanisms to Genotoxic Effects. Available at SSRN: https://ssrn.com/abstract=4150589 or http://dx.doi.org/10.2139/ssrn.4150589

Marta Martins (Contact Author)

affiliation not provided to SSRN ( email )

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Isabella Bramatti

affiliation not provided to SSRN ( email )

No Address Available

Beatriz Matos

affiliation not provided to SSRN ( email )

No Address Available

Neusa Figueiredo

affiliation not provided to SSRN ( email )

No Address Available

Pedro Pousão-Ferreira

affiliation not provided to SSRN ( email )

No Address Available

Vasco Branco

affiliation not provided to SSRN ( email )

No Address Available

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