Interactions between polycyclic aromatic hydrocarbons in binary mixtures: effects on gene expression and DNA adduct formation in precision-cut rat liver slices

Mutagenesis
Yvonne C M StaalJoost H M van Delft

Abstract

Although exposure to polycyclic aromatic hydrocarbons (PAHs) occurs mostly through mixtures, hazard and risk assessment are mostly based on the effects caused by individual compounds. The objective of the current study was to investigate whether interactions between PAHs occur, focusing on gene expression (as measured by cDNA microarrays) and DNA adduct formation. The effects of benzo[a]pyrene or dibenzo[a,h]anthracene (DB[a,h]A) alone and in binary mixtures with another PAH (DB[a,h]A, benzo[b]fluoranthene, fluoranthene or dibenzo[a,l]pyrene) were investigated using precision-cut rat liver slices. All compounds significantly modulated the expression of several genes, but overlap between genes affected by the mixture and by the individual compounds was relatively small. All mixtures showed an antagonistic response on total gene expression profiles. Moreover, at the level of individual genes, mostly antagonism was evident, with additivity and synergism observed for only a few genes. As far as DNA adduct formation is concerned, the binary mixtures generally caused antagonism. The effects in liver slices suggest a lower carcinogenic potency of PAH mixtures than estimated based on additivity of individual compounds.

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Citations

Jan 31, 2012·Environmental Science & Technology·Rolf AltenburgerBeate I Escher
Apr 22, 2009·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Kai K LiePål A Olsvik
Jul 11, 2012·Journal of Applied Toxicology : JAT·Saura C SahuRobert L Sprando
Aug 25, 2015·Biochemical and Biophysical Research Communications·Hyung Gyun KimHye Gwang Jeong
May 20, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Camille GeniesThierry Douki
Sep 12, 2015·Risk Analysis : an Official Publication of the Society for Risk Analysis·Stacey J Gaskill, Erica D Bruce
Oct 28, 2017·Frontiers in Chemistry·Nitika SinghBechan Sharma
Apr 30, 2021·Saudi Journal of Biological Sciences·Nabila E AbdelmeguidAhmed S Sultan

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