Intracellular lipoproteins as carriers for 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo(a)pyrene in rat and mouse liver.
The possible role of hepatic lipoproteins as intracellular carriers in the transport of 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo(a)pyrene was assessed by in vitro and in vivo studies. Following administration of [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin or unlabelled 2,3,7,8-tetrachlorodibenzofuran to C57 BL/6 mice or Sprague-Dawley rats these compounds were bound to lipoproteins which subsequently underwent rapid and pronounced degradative processing, possibly catalysed by lipoprotein lipase, to heavier entities. At the highest doses of xenobiotics administered, an almost complete disappearance of lipoprotein particles was observed. The in vitro incubation of [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin-lipoprotein and [3H]benzo(a)pyrene-lipoprotein complexes with separated Ah receptor and 4S protein, respectively, demonstrated that a passive transfer occurred; the latter was likely dependent on both the relative affinities of the ligands towards the different cellular binding components as well as on their quantitative binding capacity. Taken together, these findings support the idea of a carrier-role for lipoproteins in the intracellular transport of hydrophobic xenobiotics and it may be asked whether the widespread modulators of lipoprotein level such as fibrates or others affect drug transfer or action.
Souès
S
S
Laboratoire de Pharmacologie et de Toxicologie Fondamentales, Toulouse, France.
Fernandez
N
N
Souverain
P
P
Lesca
P
P
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001572:Benzofurans / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004147:Dioxins / Q000378:metabolism*; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000378:metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000378:metabolism
D001572:Benzofurans; D002352:Carrier Proteins; D004147:Dioxins; D008074:Lipoproteins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D001564:Benzo(a)pyrene; C014211:2,3,7,8-tetrachlorodibenzofuran