The non-covalent binding of benzo[a]pyrene and its hydroxylated metabolites to intracellular proteins and lipid bilayers.

Abstract:

:The non-covalent interactions of benzo[a]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 v/c (where v = 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-Hydroxybenzo[a]pyrene (BP-3-phenol), 4,5-dihydro-4,5-dihydroxybenzo[a]pyrene (BP-4,5-dihydrodiol) and 7,8-dihydro-7,8-dihydroxybenzo[a]pyrene (BP-7,8-dihydrodiol) bind more strongly (v/c = 10(5)-5 x 10(5) l x mol-1) to all three binders than does BP itself (v/c = 10(4)-7 x 10(4) l x mol-1). 9,10-Dihydro-9,10-dihydroxybenzo[a]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 (v/c = 10(4) and 3 x 10(4) x 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.

journal_name

Chem Biol Interact

authors

Tipping E,Moore BP,Jones CA,Cohen GM,Ketterer B,Bridges JW

doi

10.1016/0009-2797(80)90096-4

subject

Has Abstract

pub_date

1980-11-01 00:00:00

pages

291-304

issue

3

eissn

0009-2797

issn

1872-7786

pii

0009-2797(80)90096-4

journal_volume

32

pub_type

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