Archives of Toxicology

, Volume 64, Issue 4, pp 285–290 | Cite as

Comparative uptake, vascular transport, and cellular internalization of aflatoxin-B1 and benzo(a)pyrene

  • D. L. Busbee
  • J. O. Norman
  • R. L. Ziprin
Original Articles


Studies of the uptake of benzo(a)pyrene (BaP) and aflatoxin-B1 (AFB1) after gastric instillation showed that BaP was absorbed via the intestinal lymphatic drainage and transported to the vascular circulation sequestered within lipoproteins in thoracic duct lymph, while AFB1 was absorbed with water soluble compounds into the gastrointestinal venous drainage and was not transported in association with lipoproteins. BaP was taken up into plasma lipoproteins over a broad concentration range, while AFB1 was not sequestered within lipoproteins over the same concentration range. Low density lipoproteins (LDL) facilitated BaP uptake into fibroblasts and impeded BaP uptake into hepatocytes. High density lipoproteins (HDL) facilitated BaP uptake into hepatocytes and impeded BaP uptake into fibroblasts. The uptake of AFB1 into either fibroblasts or hepatocytes was not affected by lipoproteins.

Key words

Aflatoxin-B1 Benzo(a)pyrene Vascular transport Lipoproteins Cellular internalization 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alam SS, Solen KA, Layman DL, Riddle MD, Connor WE (1980) The mass uptake of cholesterol ester from low density lipoproteins by cultured smooth muscle and adventitial cells of human aortas. Circ Res 47: 374–383PubMedGoogle Scholar
  2. Brown MS, Anderson RGW, Goldstein JL (1983) Recycling receptors: the round trip itinerary of migrant membrane proteins. Cell 32: 662–667Google Scholar
  3. Busbee DL, Payne DM, Jasheway DW, Carlisle S, Lacko AG (1981) Separation and detection of lipoproteins in human serum by use of size-exclusion liquid chromatography: a preliminary report. Clin Chem 27: 2052–2059PubMedGoogle Scholar
  4. Busbee DL, Rankin PW, Payne DM, Jasheway DW (1982) Binding of benzo[a]pyrene and intracellular transport of a bound electrophilic benzo[a]pyrene metabolite by lipoproteins. Carcinogenesis 3 (10): 1107–1112PubMedGoogle Scholar
  5. Busbee DL, Joe CO, Ranklin PW, Ziprin RL, Wilson RD (1984) Benzo[a]pyrene uptake by lymph: a possible transport mode for immunosuppressive chemicals. J Toxicol Environ Health 13: 43–51PubMedGoogle Scholar
  6. Chalmer JG (1955) The adsorption of 3,4-benzopyrene and its fluorescent metabolites on serum proteins. Br J Cancer 9: 320–326PubMedGoogle Scholar
  7. Chen TC, Bradley WA, Gotto AM Jr, Morrisett JD (1979) Binding of the chemical carcinogenp-dimethylamino-azobenzene, by plasma low density lipoproteins. FEBS Lett 104: 236–240PubMedGoogle Scholar
  8. Coulombe RA Jr, Wilson DW, Hsieh DPH (1984) Metabolism, DNA binding, and cytotoxicity of aflatoxin B1 in tracheal explants from Syrian hamster. Toxicology 32: 117–130PubMedGoogle Scholar
  9. Dashek WV, Barker SM, Statkiewicz WR, Shanks ET (1982) Histochemical analysis of liver cells from short term, aflatoxin-dosed and nondosedCoturnix coturnix japonica. 1. Aflatoxin-sensitive quail. Poultry Science 62: 2347–2359Google Scholar
  10. Franklin RB, Elcombe CR, Vodicnik MJ, Lechw JJ (1980) Comparative aspects of the disposition and metabolism of xenobiotics in fish and mammals. Fed Proc 39 (13): 3144–3149PubMedGoogle Scholar
  11. Goldstein JL, Brown MS (1974) Binding and degradation of low density lipoproteins by cultured human fibroblasts. J Biol Chem 249: 5153–5162PubMedGoogle Scholar
  12. Goldstein JL, Ho YK, Basu SK, Brown MS (1979) Binding sites on macrophages that mediate uptake and degradation of acetylated low density lipoproteins, producing massive cholesterol deposition. Proc Natl Acad Sci USA 76: 333–337PubMedGoogle Scholar
  13. Grubbs CJ, Moon RC (1973) Transport of orally administered 9, 10-dimethyl-1,2-benzanthracene in the Sprague-Dawley rat. Cancer Res 33: 1785–1789PubMedGoogle Scholar
  14. Hanigan HM, Laishes BA (1984) Toxicity of aflatoxin B1 in rat and mouse hepatocytes in vivo and in vitro. Toxicology 30: 185–193PubMedGoogle Scholar
  15. Irvin TR, Wogan GN (1984) Quantitation of aflatoxin B1 adduction within the ribosomal RNA gene sequences of rat liver DNA. Proc Natl Acad Sci USA 81: 664–668PubMedGoogle Scholar
  16. Kaminski NE, Wells DS, Dauterman WC, Roberts JF, Guthrie FE (1986) Macrophage uptake of a lipoprotein-sequestered toxicant: A potential route of immunotoxicity. Toxicol Appl Pharmacol 82 (3): 474–480PubMedGoogle Scholar
  17. Keenan RW, Kruczek ME, Fischer JB (1977) The binding of [3H]-dolichol by plasma high density lipoproteins. Biochim Biophys Acta 486: 1–9Google Scholar
  18. Kocan RM, Chi EY, Eriksen N, Benditt EP, Landolt ML (1983) Sequestration and release of polycyclic aromatic hydrocarbons by vertebrate cells in vitro. Environ Mutagen 5: 647–656Google Scholar
  19. Kotin P, Falk HL, Busser R (1959) Distribution, retention, and elimination of [14C]-3,4-benzopyrene after administration to mice and rats. J Natl Cancer Inst 23: 541–555Google Scholar
  20. Maliwal BP, Guthrie FE (1981) Interaction of insecticides with human plasma lipoproteins. Chem Biol Interact 35 (2): 177–188PubMedGoogle Scholar
  21. Maliwal BP, Guthrie FE (1982) In vitro uptake and transfer of chlorianted hydrocarbons among human lipoproteins. J Lipid Res 23: 474–479PubMedGoogle Scholar
  22. McQueen CA, Kreiser DM, Williams GM (1983) The hepatocyte primary culture/DNA repair assay using mouse or hamster hepatocytes. Environ Mutagen 5: 1–8Google Scholar
  23. O'Brien K, Moss E, Judah D, Neal G (1983) Metabolic basis of the species difference to aflatoxin B1-induced hepatotoxicity. Biochem Biophys Res Commun 114 (2): 813–821PubMedGoogle Scholar
  24. Plant AL, Benson DM, Smith LC (1985) Cellular uptake and intracellular localization of benzo(a)pyrene by digital fluorescence microscopy. J Cell Biol 100: 1925–1308Google Scholar
  25. Poland A, Glover E, Kende AS (1976) Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. J Biol Chem 251: 4936–4945PubMedGoogle Scholar
  26. Remsen J, Shireman R (1981) Effect of low density lipoprotein on the incorporation of benzo(a)pyrene by cultured cells. Cancer Res 41: 3179–3185PubMedGoogle Scholar
  27. Salocks CB, Hsieh DP, Byard JL (1981) Butylated hydroxytoluene pretreatment protects against cytotoxicity and reduces covalent binding of aflatoxin B1 in primary hepatocyte cultures. Pharmacol Appl Toxicol 59: 331–345Google Scholar
  28. Shireman RB, Schneider M (1982) Association of aflatoxin B1 with plasma components in vitro. Toxicol Lett 14: 213–220PubMedGoogle Scholar
  29. Shireman RB, Kilgore LL, Fisher WR (1977) Solubilization of apolipoprotein B and its specific binding by the cellular receptor for low density lipoprotein. Proc Natl Acad Sci USA 74: 5150–5154PubMedGoogle Scholar
  30. Shu HP, Nichols AV (1979) Benzo[a]pyrene uptake by human plasma lipoproteins in vitro. Cancer Res 39: 1224–1230PubMedGoogle Scholar
  31. Wandel M, Norum KR, Berg T, Ose L (1981) Binding, uptake, and degradation of [125I]-labeled high-density lipoproteins in isolated non-parenchymal rat liver cells. Scand J Gastroenterol 16: 1–10PubMedGoogle Scholar
  32. Weisberger JH, Grantham PH, Weisberger EK (1969) The transport of chemical carcinogens by blood. In: Bergmann ED, Pullman B (eds) The Jerusalem Symposium on Quantum Chemistry and Biochemistry, Physico-Chemical Mechanisms of Carcinogenesis. Vol. 1 pp 262–283Google Scholar
  33. Wilson RD, Ziprin RL, Clark DE, Ellissalde MH (1982) Absorption of pentachlorophenol by the ovine lymphatic system: a technical note Vet Hum Toxicol 24 (1): 12–15PubMedGoogle Scholar
  34. Wilson RD, Ziprin RL, Ragsdale S, Busbee DL (1985) Uptake and vascular transport of ingested aflatoxin-B1. Toxicol Lett 29: 169–176PubMedGoogle Scholar
  35. Wong ZA, Hsieh DPH (1980) The comparative metabolism and toxicokinetics of aflatoxin B1 in the monkey, rat, and mouse. Toxicol Appl Pharmacol 55: 115–125PubMedGoogle Scholar
  36. Yoo JS, Norman JO, Busbee DL (1984) Uptake of benzo[a]pyrene into human lipoproteins: triglyceride content as the determining factor Exp Biol Med 177: 434–440Google Scholar
  37. Ziprin RL, Ellissalde MH, Clark DE, Wilson RD (1980) Absorption of polychlorinated biphenyl by the ovine lymphatic system. Vet Hum Toxicol 22 (5): 304–308Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • D. L. Busbee
    • 1
    • 2
  • J. O. Norman
    • 1
  • R. L. Ziprin
    • 3
  1. 1.Division of Cell Biology, Department of Anatomy, College of Veterinary MedicineTexas A&M UniversityCollege StationUSA
  2. 2.Division of Toxicology, Department of Physiology and Pharmacology, College of Veterinary MedicineTexas A&M UniversityCollege StationUSA
  3. 3.Veterinary Toxicology and Entomology Research LaboratoryARS, USDACollege StationUSA

Personalised recommendations