Print Email Facebook Twitter Binary PAH mixtures cause additive or antagonistic effects on gene expression but synergistic effects on DNA adduct formation Title Binary PAH mixtures cause additive or antagonistic effects on gene expression but synergistic effects on DNA adduct formation Author Staal, Y.C.M. Hebels, D.G.A.J. van Herwijnen, M.H.M. Gottschalk, R.W.H. van Schooten, F.J. van Delft, J.H.M. TNO Kwaliteit van Leven Publication year 2007 Abstract Polycyclic aromatic hydrocarbons (PAHs) cover a wide range of structurally related compounds which differ greatly in their carcinogenic potency. PAH exposure usually occurs through mixtures rather than individual compounds. Therefore, we assessed whether the effects of binary PAH mixtures on gene expression, DNA adduct formation, apoptosis and cell cycle are additive compared with the effects of the individual compounds in human hepatoma cells (HepG2). Equimolar and equitoxic mixtures of benzo[a]pyrene (B[α]P) with either dibenzo[a,l]pyrene (DB[a,l]P), dibenzo[a,h]anthracene (DB[a,h]A), benzo[b]fluoranthene (B[b]F), fluoranthene (FA) or 1-methylphenanthrene (1-MPA) were studied. DB[a,l]P, B[α]P, DB[a,h]A and B[b]F dose-dependently increased apoptosis and blocked cells cycle in S-phase. PAH mixtures showed an additive effect on apoptosis and on cell cycle blockage. DNA adduct formation in mixtures was higher than expected based on the individual compounds, indicating a synergistic effect of PAH mixtures. Equimolar mixtures of B[α]P and DB[a,l]P (0.1, 0.3 and 1.0 μM) were assessed for their effects on gene expression. Only at 1.0 μM, the mixture showed antagonism. All five compounds were also tested as a binary mixture with B[α]P in equitoxic concentrations. The combinations of B[α]P with B[b]F, DB[a,h]A or FA showed additivity, whereas B[α]P with DB[a,l]P or 1-MPA showed antagonism. Many individual genes showed additivity in mixtures, but some genes showed mostly antagonism or synergism. Our results show that the effects of binary mixtures of PAHs on gene expression are generally additive or slightly antagonistic, suggesting no effect or decreased carcinogenic potency, whereas the effects on DNA adduct formation show synergism, which rather indicates increased carcinogenic potency. © The Author 2007. Published by Oxford University Press. All rights reserved. Subject Toxicology and Applied Pharmacologybenzo[a]pyrenebenzo[b]fluoranthenedibenz[a,h]anthracenedibenzo[a,l]pyrenefluoranthenephenanthrene derivativepolycyclic aromatic hydrocarbonapoptosisarticlecarcinogenesiscarcinogenicitycell cyclecell strain HepG2controlled studyDNA adductexposuregene expressionhepatoma cellhumanhuman cellnucleotide sequencepriority journalunindexed sequenceAir PollutantsApoptosisCell CycleCell Line, TumorDNA AdductsDrug AntagonismDrug SynergismGene Expression ProfilingGene Expression Regulation, NeoplasticHumansPolycyclic Hydrocarbons, Aromatic To reference this document use: http://resolver.tudelft.nl/uuid:97ecf66c-bf10-473c-8b27-b6a18afbb998 DOI https://doi.org/10.1093/carcin/bgm182 TNO identifier 240361 ISSN 0143-3334 Source Carcinogenesis, 28 (12), 2632-2640 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.