Toxic and Genotoxic Effects of Mixtures of Polycyclic Aromatic Hydrocarbons

Donnelly, K.C.; Naufal, Ziad

doi:10.1002/9783527630196.ch20

Cited by 1 publication

(1 citation statement)

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“…Phenanthrene is a noncytochrome P450 1A (CYP1A)-inducing PAH, with aryl hydrocarbon receptor (AhR) independent toxicity (Pathiratne and Hemachandra, 2010;Johnson et al, 2008), while the 4-5 ring PAHs have an AhR dependent mode of action. The main toxicological effects of PAHs, however, are in their genotoxicity and potential endocrine disruption in teleosts (Donnelly and Naufal, 2010;van der Oost et al, 2003;Johnson et al, 2008). Suppressed steroid levels and steroid synthesis inhibition (Monteiro et al, 2000;Seruto et al, 2005;Yan et al, 2012) have been detected in PAH-exposed teleosts as well as retinoid signalling disruption (Benisek et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Toxicological effect of single contaminants and contaminant mixtures associated with plant ingredients in novel salmon feeds

Søfteland¹,

Kirwan

Hori

et al. 2014

Food and Chemical Toxicology

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Increasing use of plant feed ingredients may introduce contaminants not previously associated with farming of salmonids, such as pesticides and PAHs from environmental sources or from thermal processing of oil seeds. To screen for interaction effects of contaminants newly introduced in salmon feeds, Atlantic salmon primary hepatocytes were used. The xCELLigence cytotoxicity system was used to select optimal dosages of the PAHs benzo(a)pyrene and phenanthrene, the pesticides chlorpyrifos and endosulfan, and combinations of these. NMR and MS metabolic profiling and microarray transcriptomic profiling was used to identify novel biomarkers. Lipidomic and transcriptomic profiling suggested perturbation of lipid metabolism, as well as endocrine disruption. The pesticides gave the strongest responses, despite having less effect on cell viability than the PAHs. Only weak molecular responses were detected in PAH-exposed hepatocytes. Chlorpyrifos suppressed the synthesis of unsaturated fatty acids. Endosulfan affected steroid hormone synthesis, while benzo(a)pyrene disturbed vitamin D3 metabolism. The primary mixture effect was additive, although at high concentrations the pesticides acted in a synergistic fashion to decrease cell viability and down-regulate CYP3A and FABP4 transcription. This work highlights the usefulness of 'omics techniques and multivariate data analysis to investigate interactions within mixtures of contaminants with different modes of action.

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