Advertisement

Subcellular Distribution and Macromolecular Binding of Aflatoxin in Fetal and Neonatal Rat Liver

  • S. Kumagai
  • Y. Ito
  • M. Iwaki
  • A. Nagahara
  • Y. Omata

Abstract

The aflatoxins are mycotoxins produced by several species of Aspergillus, aflatoxin B1 (B1) being the most potent hepatotoxic and hepatocarcinogenic compound among these metabolites. There is a wide variation in susceptibility to B1 among animal species and sexes.23 Considerable research has been undertaken on biochemical mechanisms of the action of aflatoxin in relation to the species and sex differences. Formation of B1-8,9-epoxide by the cytochrome P-450 enzyme system and subsequent binding to DNA are regarded as critical steps of the carcinogenic effect of B1. 1,21,24,29,31 The importance of formation of the B1-glutathione conjugate by cytosolic glutathione S-transferase in inactivation of B1-epoxide has been well documented in relation to species and sex differences of the B1 effects. 3,4,18,22,27

Keywords

Subcellular Distribution Cytosolic Glutathione Hepatic Cytosol Packard Inst Hepatic Macromolecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Campbell TC, Hayes JR, 1976, The role of aflatoxin metabolism in its toxic lesion. Tox Appl Pharmacol. 35:199–222.CrossRefGoogle Scholar
  2. 2.
    Cullen JM, Ruebner BH, Hsieh LS, Hyde DM, Hsieh DP, 1987, Carcinogenicity of dietary aflatoxin M in male Fischer rats compared to aflatoxin B1. Cancer Res. 47:1913–1917.Google Scholar
  3. 3.
    Degen GH, Neumann H-G, 1978, The major metabolite of aflatoxin B1 in the rat is a glutathione conjugate. Chem-Biol Interact., 22:239–255.CrossRefGoogle Scholar
  4. 4.
    Degen GH, Neumann H-G, 1981, Differences in aflatoxin B1 susceptibility of rat and mouse are correlated with the capacity in vitro to inactivate aflatoxin B1 epoxide. Carcinogenesis, 2:299–306.CrossRefGoogle Scholar
  5. 5.
    DiPaolo JA, Elis J, Erwin HM 1967, Teratogenic response by hamsters, rats, and mice to aflatoxin B1 Nature, 215:638–639.Google Scholar
  6. 6.
    Elis J, DiPaolo JA, 1967, Aflatoxin B induction of malformations. Arch Path., 83:53–57.Google Scholar
  7. 7.
    Essigman JM, Croy RG, Bennett RA, Wogan GN, 1982, Metabolic activation of aflatoxin B1: Patterns of DNA adduct formation, removal, and execution in relation to carcinogenesis. Drug Metah Rev., 13:581–602.CrossRefGoogle Scholar
  8. 8.
    Geissler F, Faustman EM, 1988, Developmental toxicity of aflatoxin B1 in the rodent embryo in vitro: Contribution of exogenous biotransformation systems to toxicity. Teratology, 37:101–111.CrossRefGoogle Scholar
  9. 9.
    Green CE, Rice DW, Hsieh DPH, Byard JL, 1982, The comparative metabolism and toxic potency of aflatoxin B and aflatoxin M in primary cultures of adult-rat hepatocytes. Fd Chem Toxic., 20:53–60.CrossRefGoogle Scholar
  10. 10.
    Grice HC, Moodie CA, Smith DC, 1973, The carcinogenic potential of aflatoxin or its metabolites in rats from dams fed aflatoxin pre- and postpartum. Cancer Res., 33:2262–268.Google Scholar
  11. 11.
    Gurtoo HL, Dave CV, 1975, In vitro metabolic conversion of aflatoxins and benzo(a)pyrene to nucleic acid-binding metabolites. Cancer Res., 35:382–389.Google Scholar
  12. 12.
    Gurtoo HL, Motycka L, 1976, Effect of sex difference on the in vitro and in vivo metabolism of aflatoxin B by the rat. Cancer Res., 36:4663–4671.Google Scholar
  13. 13.
    Hales BF, Neims AH, 1976, Developmental aspects of glutathione S.-transferase (Ligandin) in rat liver. Biochem J., 160:231–236. Hayes AW, Cain JA, Moore BG, 1977, Effect of aflatoxin B, ochratoxin A, and rubratoxin B on infant rats. Fd Cosmet Toxic., 15:23–27.CrossRefGoogle Scholar
  14. 14.
    Homma S, Oka M, Goto N, Tomizawa M, Miura K, Imamura K, 1984, Effects of phenobarbital on the transplacental tumorigenesis by aflatoxin B1 in mice DDK strain. In: “Toxigenic Fungi-their toxins and health hazard,” Ueno Y, ed., Kodansha, Tokyo.Google Scholar
  15. 15.
    Li YK, Chu FS, 1982, Kinetics of transformation of aflatoxin B1 into aflatoxin M in lactating mouse: An ELISA analysis. Experientia, 38:842–843.CrossRefGoogle Scholar
  16. 16.
    Lijinsky W, Ross AE, 1969, Alkylation of rat liver nucleic acids not related to carcinogenesis by N-nitrosamines. J Nat Cancer Inst., 42:1095 1100.Google Scholar
  17. 17.
    Lotlikar PD, Jhee EC, Insetta SM, Clearfield MS, 1984, Modulation of microsome-mediated aflatoxin Bx binding to exogenous and endogenous DNA by cytosolic glutathione S- transferases in rat and hamster livers. Carcinogenesis, 5:269–276.CrossRefGoogle Scholar
  18. 18.
    Lutz WK, Jaggi W, Luthy J, Sagelsdorff P, Schlatter C, 1980, In vivo cova lent binding of aflatoxin B1 and aflatoxin M to liver DNA of rat, mouse and pig. Chem-Biol Interact., 32:249–z56.CrossRefGoogle Scholar
  19. 19.
    Mainigi KD, Campbell TC, 1981, Effect of sex differences on subcellular distribution of aflatoxin B in F-344 rats treated with various risk- modifying factors. Tox Appl Pharmacol., 58:236–243.CrossRefGoogle Scholar
  20. 20.
    Neal GE, Judah DJ, Stirpe F, Patterson DSP, 1981, The formation of 2, 3 -dihydroxy-2, 3 - dihydro - aflatoxin B1 by the metabolism of aflatoxin B1 by liver microsomes isolated from certain avian and mammalian species and the possible role of this metabolite in the acute toxicity of aflatoxin B1 Tox Appl Pharmacol., 58:431–437.CrossRefGoogle Scholar
  21. 21.
    Neal GE, Green JA, 1983, The requirement for glutathione S>-transferase in the conjugation of activated aflatoxin B1 during aflatoxin hepatocar-cinogenesis in the rat. Chem-Biol Interact., 45:259–275.CrossRefGoogle Scholar
  22. 22.
    Newberne PM, Butler WH, 1969, Acute and chronic effects of aflatoxin on the liver of domestic and laboratory animals: a review. Cancer Res.,29:236–250.Google Scholar
  23. 23.
    O’Brien K, Moss E, Judah D, Neal G, 1983, Metabolic basis of the species difference to aflatoxin induced hepatotoxicity. Biochem Biophys Res Commun., 114:813–821.CrossRefGoogle Scholar
  24. 24.
    Pong RS, Wogan GN, 1971, Toxicity and biochemical and fine structural effects of synthetic aflatoxins M and B in rat liver. J Nat Cancer Inst., 47:585–592.Google Scholar
  25. 25.
    Portman RS, Plowman KM, Campbell TC, 1970, On mechanisms affecting species susceptibility to aflatoxin. Biochim Biophys Acta, 208:487–495. Raj HG, Clearfield MS, Lotlikar PD, 1984, Comparative kinetic studies on aflatoxin B -DNA binding and aflatoxin B -glutathione conjugation with rat ana hamster livers in vitro. Carcinogenesis, 5:879–884.CrossRefGoogle Scholar
  26. 26.
    Schmidt RE, Panciera RJ, 1980, Effects of aflatoxin on pregnant hamsters and hamster foetuses. J Comp Path., 90:339–347.CrossRefGoogle Scholar
  27. 27.
    Swenson DH, Lin J-K, Miller ED, Miller JA, 1977, Aflatoxin B1–2,3-oxide as a probable intermediate in the covalent binding of aflatoxins B and B to rat liver DNA and ribosomal RNA in vivo. Cancer Res., 37:172–181.Google Scholar
  28. 28.
    Trucksess MW, Richard JL, Stoloff L, McDonald JS, Brumley WC, 1983, Absorption and distribution patterns of aflatoxicol and aflatoxins B1 and M in blood and milk of cows given aflatoxin B. Am J Vet Res., 44:1732–1756.Google Scholar
  29. 29.
    Ueno I, Friedman L, Stone CL, 1980, Species difference in the binding of aflatoxin B to hepatic macromolecules. Tox Appl Pharmacol., 52:177–180.CrossRefGoogle Scholar
  30. 30.
    Vesselinovitch SD, Mihailovich N, Wogan GN, Lombard LS, Rao KVN, 1972, Aflatoxin B, a hepatocarcinogen in the infant mouse. Cancer Res., 32:2289–2291.Google Scholar
  31. 31.
    Wogan GN, Edwards GS, Newberne PM, 1971, Structure-activity relationship in toxicity and carcinogenicity of aflatoxins and analogs. Cancer Res., 31:1936–1942.Google Scholar
  32. 32.
    Wogan GN, Paglialunga S, 1974, Carcinogenicity of synthetic aflatoxin M1 in rats. Fd Cosmet Toxic., 12:381–384.CrossRefGoogle Scholar
  33. 33.
    Wong ZA, Hsieh DPH, 1980, The comparative metabolism and toxicokinetics of aflatoxin B in the monkey, rat, and mouse. Tox Appl Pharmacol., 55:115–125.CrossRefGoogle Scholar
  34. 34.
    Yoshizawa H, Uchimaru R, Kamataki T, Kato R, Ueno Y, 1982, Metabolism and activation of aflatoxin B by reconstituted cytochrome P-450 system of rat liver. Cancer Res., 42:1120–1124.Google Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • S. Kumagai
    • 1
  • Y. Ito
    • 1
  • M. Iwaki
    • 1
  • A. Nagahara
    • 1
  • Y. Omata
    • 1
  1. 1.National Institute of HealthTokyoJapan

Personalised recommendations