Pushparajah, DS, Plant, KE, Plant, NJ orcid.org/0000-0003-4332-8308 et al. (1 more author) (2017) Synergistic and antagonistic interactions of binary mixtures of polycyclic aromatic hydrocarbons in the upregulation of CYP1 activity and mRNA levels in precision-cut rat liver slices. Environmental Toxicology, 32 (3). pp. 764-775. ISSN 1520-4081
Abstract
The current studies investigate whether synergistic or antagonistic interactions in the upregulation of CYP1 activity occur in binary mixtures of polycyclic aromatic hydrocarbons (PAHs) involving benzo[a]pyrene and five other structurally diverse PAHs of varying carcinogenic activity. Precision-cut rat liver slices were incubated with benzo[a]pyrene alone or in combination with a range of concentrations of a second PAH, and ethoxyresorufin O-deethylase, CYP1A1 and CYP1B1 mRNA levels determined. Concurrent incubation of benzo[a]pyrene with either dibenzo[a,h]anthracene or fluoranthene in liver slices led to a synergistic interaction, at least at low concentrations, in that ethoxyresorufin O-deethylase activity was statistically higher than the added effects when the slices were incubated with the individual compounds. In contrast, benzo[b]fluoranthene and, at high doses only, dibenzo[a,l]pyrene gave rise to antagonism, whereas 1-methylphenanthrene had no effect at all concentrations studied. When CYP1A1 mRNA levels were monitored, benzo[b]fluoranthene gave rise to an antagonistic response when incubated with benzo[a]pyrene, whereas all other compounds displayed synergism, with 1-methylphenathrene being the least effective. A similar picture emerged when CYP1B1 mRNA levels were determined, though the effects were less pronounced. In conclusion, it has been demonstrated that the benzo[a]pyrene-mediated upregulation of CYP1, at the mRNA and activity levels, is synergistically and antagonistically modulated by other PAHs.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Wiley Periodicals, Inc. This is the peer reviewed version of the following article: Pushparajah, D. S., Plant, K. E., Plant, N. J. and Ioannides, C. (2017), Synergistic and antagonistic interactions of binary mixtures of polycyclic aromatic hydrocarbons in the upregulation of CYP1 activity and mRNA levels in precision-cut rat liver slices. Environ. Toxicol., 32: 764–775. doi:10.1002/tox.22276; which has been published in final form at https://doi.org/10.1002/tox.22276. This article may be used for non-commercial purposes in accordance with the Wiley Terms and Conditions for Self-Archiving. |
Keywords: | polycyclic aromatic hydrocarbons; cytochrome P450; interactions; risk assessment; precision-cut tissue slices |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 30 Jun 2017 08:31 |
Last Modified: | 07 Feb 2018 08:47 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/tox.22276 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:118393 |