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Interactions Between Polycyclic Aromatic Hydrocarbons in the Liver.

Pushparajah, Daphnee S. (2006) Interactions Between Polycyclic Aromatic Hydrocarbons in the Liver. Doctoral thesis, University of Surrey (United Kingdom)..

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Utilising precision-cut rat and human slices, it was demonstrated that individual polycyclic aromatic hydrocarbons (PAHs) are capable of elevating CYP1A1, epoxide hydrolase and glutathione S-transferase mRNA levels and enzyme activity, but to markedly varying extents. It appears that the rat might be a good surrogate animal to human, as far as modulation of CYP1A1 by PAHs is concerned, though some differences were noted in the case of epoxide hydrolase and glutathione S-transferase activity in the two species. There was a positive correlation between binding to the Ah receptor and CYP1A1 modulating potency of PAHs in rat slices, confirming that potent PAHs act as good ligands for this receptor. In interaction studies, exposure of rat slices to binary PAHs mixtures revealed that benzo(a)pyrene-induced CYP1A1 activity was modulated by the presence of other PAHs, both synergistically and antagonistically, and these interactions led to corresponding changes in the metabolism of benzo(a)pyrene to phenols and in the formation of benzo(a)pyrene-DNA adducts. At the mRNA level, in the presence of benzo(a)pyrene, all PAHs caused interactions, either synergistic or antagonistic, in CYP1A1, CYP1B1, epoxide hydrolase and glutathione S-transferase, which were not always paralleled by similar changes in corresponding enzyme activities.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Pushparajah, Daphnee S.
Date : 2006
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 2006.
Depositing User : EPrints Services
Date Deposited : 06 May 2020 14:37
Last Modified : 06 May 2020 14:45

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