The non-covalent binding of benzo[a]pyrene and its hydroxylated metabolites to intracellular proteins and lipid bilayers |
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Authors: | E Tipping BP Moore Carol A Jones GM Cohen B Ketterer JW Bridges |
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Institution: | 1. Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School, London, W1P 7PN, United Kingdom;2. Department of Biochemistry, University of Surrey, Guildford, Surrey, GU2 5XH United Kingdom;3. Institute of Industrial & Environmental Health & Safety, University of Surrey, Guildford, Surrey, GU2 5XH United Kingdom |
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Abstract: | The non-covalent interactions of benzoa]pyrene (BP) and several of its hydroxylated metabolites with ligandin, aminoazodye-binding protein A (Z-protein, fatty acid binding protein) and lecithin bilayers have been studied by equilibrium dialysis, an adsorption technique and fluorescence spectroscopy. Binding affinities expressed as (where = moles of BP or BP metabolite bound per mole of protein or lipid and c = unbound concentration), were measured at concentrations sufficiently low that there was no self-association of the unbound compounds as judged by their fluorescence characteristics. 3-Hydroxybenzoa]pyrene (BP-3-phenol), 4,5-dihydro-4,5-dihydroxybenzoa]pyrene (BP-4,5-dihydrodiol) and 7,8-dihydro-7,8-dihydroxybenzoa]pyrene (BP-7,8-dihydrodiol) bind more strongly () to all three binders than does BP itself (). 9,10-Dihydro-9,10-dihydroxybenzoa]pyrene (BP-9,10-dihydrodiol) binds to ligandin with an affinity similar to those of the other BP metabolites studied here, but binds much less strongly to both protein A and lecithin ( and 3 · 104 l · mol?1, respectively). The low affinity of BP-9,10-dihydrodiol for lecithin would account for earlier findings that on incubation of BP with isolated rat hepatocytes, this metabolite egressed from the cells to the extracellular medium much more readily than either BP-4,5-dihydrodiol or BP-7,8-dihydrodiol.Calculations based on these results suggest that within hepatocytes BP and its metabolites, including BP-9,10-dihydrodiol, will be found almost exclusively associated (>98%) with lipid membranes. |
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Keywords: | BP BP-3-phenol BP-4 5-dihydrodiol BP-7 8-dihydrodiol BP-9 10-dihydrodiol To whom correspondence should be sent |
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