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Mutagenesis Advance Access published online on August 18, 2008
Mutagenesis, doi:10.1093/mutage/gen041
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© The Author 2008. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

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

Yvonne C. M. Staal1, Daphnee S. Pushparajah2, Marcel H. M. van Herwijnen, Ralph W. H. Gottschalk, Lou M. Maas, Costas Ioannides2, Frederik J. van Schooten and Joost H. M. van Delft*

Department of Health Risk Analysis and Toxicology, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands 2Molecular Toxicology Group, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK 1Present address: TNO Quality of Life, Department of Toxicology and Applied Pharmacology, PO Box 360, 3700 AJ Zeist, The Netherlands

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.

* To whom correspondence should be addressed. Tel: +31 43 3881092; Fax: +31 43 3884146; E-mail: J.vanDelft{at}GRAT.unimaas.nl

Received on January 10, 2008; revised on May 8, 2008; accepted on May 16, 2008.


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