Systemic excretion of benzo(a)pyrene in the control and microsomally induced rat: the influence of plasma lipoproteins and albumin as carrier molecules.
In vitro studies have previously indicated that benzo(a)pyrene distributes primarily into the plasma lipoprotein fraction when incubated with whole plasma. Hydroxylated metabolites of benzo(a)pyrene distribute increasingly into the albumin fraction as the degree of metabolite hydroxylation increases. This report assesses the influence of plasma lipoproteins and albumin as carriers for benzo(a)pyrene on carcinogen excretion in the control and microsomally induced rat. Male Sprague-Dawley rats cannulated in the bile duct received i.v. injections of radiolabeled benzo(a)pyrene noncovalently bound to the very-low-density, low-density, or high-density lipoproteins in equimolar amounts. Bile was collected and measured for radioactivity. Cumulative biliary excretions of benzo(a)pyrene complexed with rat lipoproteins were 39.6 +/- 9.7 (S.D.), 24.6 +/- 1.3, and 21.2 +/- 8.8% for very low-density, low-density, and high-density lipoprotein, respectively. Values for excretion of benzo(a)pyrene complexed with rat or human lipoproteins were comparable. These data suggest that the transport molecule can effect a 2-fold difference in benzo(a)pyrene excretion under conditions of the present study. We infer that metabolism of the plasma lipoprotein molecules determines, in part, the extent of benzo(a)pyrene excretion. Cumulative biliary excretions of albumin-bound benzo(a)pyrene, 3-hydroxybenzo(a)pyrene, benzo(a)pyrene 7,8-dihydrodiol, and benzo(a)pyrene-4,5-epoxide were 28.0 +/- 2.7, 39.8 +/- 0.5, 46.9 +/- 2.5, and 49.8 +/- 1.2%, respectively. Thus, excretion increased as the degree of benzo(a)pyrene hydroxylation increased. The effect of microsomal enzyme induction on excretion of lipoprotein-bound benzo(a)pyrene was also assessed. Contrary to expectation, excretion of benzo(a)pyrene bound to the very-low-density, low-density, or high-density lipoproteins in Aroclor-induced rats was not greater than that of control animals. Hence, under the conditions of the present study, 60 to 80% of the injected benzo(a)pyrene and 50 to 60% of the injected benzo(a)pyrene metabolites were not excreted immediately in control or microsomally induced animals. This benzo(a)pyrene may represent a carcinogen pool that is slowly excreted.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000378:metabolism*; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism*; D014316:Tritium
D001140:Aroclors; D001580:Benzopyrenes; D002250:Carbon Radioisotopes; D002273:Carcinogens; D008074:Lipoproteins; D012709:Serum Albumin; D014316:Tritium; D020111:Chlorodiphenyl (54% Chlorine); D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital