pmc.ncbi.nlm.nih.gov

Identification of the principal aflatoxin B1-DNA adduct formed in vivo in rat liver

Abstract

The products of in vivo covalent binding of activated aflatoxin B1 (AFB1) to DNA have been investigated in rats. The principal covalent product formed in liver DNA of rats treated with AFB1 has been identified as 2,3-dihydro-2-(N7-guanyl)-3-hydroxy-aflatoxin B1. This compound was isolated from the liver DNA of rats dosed with AFB1 (2.0 mg/kg) in sufficient quantity for characterization by physicochemical techniques, including field-desorption mass spectrometry. This information together with results of chemical methylation of the compound proved that the major adduct formed between DNA and AFB1 in vivo is identical to that produced in vitro when AFB1 is incubated with DNA in the presence of a rat liver microsomal activating system. Quantitative studies of formation of this compound revealed a dose-dependent relationship between the level of its occurence in liver DNA and AFB1 doses over the range 0.125-1.0 mg/kg.

1745

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ASAO T., BUECHI G., ABDEL-KADER M. M., CHANG S. B., WICK E. L., WOGAN G. N. THE STRUCTURES OF AFLATOXINS B AND G. J Am Chem Soc. 1965 Feb 20;87:882–886. doi: 10.1021/ja01082a031. [DOI] [PubMed] [Google Scholar]
  2. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BUTLER W. H. ACUTE TOXICITY OF AFLATOXIN B-1 IN RATS. Br J Cancer. 1964 Dec;18:756–762. doi: 10.1038/bjc.1964.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Büchi G., Foulkes D. M., Kurono M., Mitchell G. F., Schneider R. S. The total synthesis of racemic aflatoxin B1. J Am Chem Soc. 1967 Dec 6;89(25):6745–6753. doi: 10.1021/ja01001a062. [DOI] [PubMed] [Google Scholar]
  5. Essigmann J. M., Croy R. G., Nadzan A. M., Busby W. F., Jr, Reinhold V. N., Büchi G., Wogan G. N. Structural identification of the major DNA adduct formed by aflatoxin B1 in vitro. Proc Natl Acad Sci U S A. 1977 May;74(5):1870–1874. doi: 10.1073/pnas.74.5.1870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Friedman M. A., Wogan G. N. Liver nuclear RNA metabolism in rats treated with aflatoxin B1. Life Sci II. 1970 Jul 8;9(13):741–747. doi: 10.1016/0024-3205(70)90290-0. [DOI] [PubMed] [Google Scholar]
  7. Garner R. C. Microsome-dependent binding of aflatoxin B1 to DNA, RNA, polyribonucleotides and protein in vitro. Chem Biol Interact. 1973 Feb;6(2):125–129. doi: 10.1016/0009-2797(73)90079-3. [DOI] [PubMed] [Google Scholar]
  8. Garner R. C., Wright C. M. Binding of [-14C]aflatoxin B1 to cellular macromolecules in the rat and hamster. Chem Biol Interact. 1975 Aug;11(2):121–131. doi: 10.1016/0009-2797(75)90019-8. [DOI] [PubMed] [Google Scholar]
  9. Garner R. C., Wright C. M. Induction of mutations in DNA-repair deficient bacteria by a liver microsomal metabolite of aflatoxin B1. Br J Cancer. 1973 Dec;28(6):544–551. doi: 10.1038/bjc.1973.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. HYMER W. C., KUFF E. L. ISOLATION OF NUCLEI FROM MAMMALIAN TISSUES THROUGH THE USE OF TRITON X-100. J Histochem Cytochem. 1964 May;12:359–363. doi: 10.1177/12.5.359. [DOI] [PubMed] [Google Scholar]
  11. Hecht S. M., Adams B. L., Kozarich J. W. Chemical transformations of 7,9-disubstituted purines and related heterocycles. Selective reduction of imines and immonium salts. J Org Chem. 1976 Jun 25;41(13):2303–2311. doi: 10.1021/jo00875a019. [DOI] [PubMed] [Google Scholar]
  12. Krahn D. F., Heidelberger C. Liver homogenate-mediated mutagenesis in chinese hamster V79 cells by polycyclic aromatic hydrocarbons and aflatoxins. Mutat Res. 1977 Feb 1;46(1):27–44. doi: 10.1016/0165-1161(77)90108-x. [DOI] [PubMed] [Google Scholar]
  13. LAWLEY P. D., BROOKES P. FURTHER STUDIES ON THE ALKYLATION OF NUCLEIC ACIDS AND THEIR CONSTITUENT NUCLEOTIDES. Biochem J. 1963 Oct;89:127–138. doi: 10.1042/bj0890127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lafarge C., Frayssinet C. The reversibility of inhibition of RNA and DNA synthesis induced by aflatoxin in rat liver. A tentative explanation for carcinogenic mechanism. Int J Cancer. 1970 Jul 15;6(1):74–83. doi: 10.1002/ijc.2910060112. [DOI] [PubMed] [Google Scholar]
  15. Lin J. K., Miller J. A., Miller E. C. 2,3-Dihydro-2-(guan-7-yl)-3-hydroxy-aflatoxin B1, a major acid hydrolysis product of aflatoxin B1-DNA or -ribosomal RNA adducts formed in hepatic microsome-mediated reactions and in rat liver in vivo. Cancer Res. 1977 Dec;37(12):4430–4438. [PubMed] [Google Scholar]
  16. MASTER R. W. POSSIBLE SYNTHESIS OF POLYRIBONUCLEOTIDES OF KNOWN BASE-TRIPLET SEQUENCES. Nature. 1965 Apr 3;206:93–93. doi: 10.1038/206093b0. [DOI] [PubMed] [Google Scholar]
  17. Martin C. N., Garner R. C. Aflatoxin B -oxide generated by chemical or enzymic oxidation of aflatoxin B1 causes guanine substitution in nucleic acids. Nature. 1977 Jun 30;267(5614):863–865. doi: 10.1038/267863a0. [DOI] [PubMed] [Google Scholar]
  18. Pong R. S., Wogan G. N. Time course and dose-response characteristics of aflatoxin B1 effects on rat liver RNA polymerase and ultrastructure. Cancer Res. 1970 Feb;30(2):294–304. [PubMed] [Google Scholar]
  19. Rogers A. E., Newberne P. M. The effects of aflatoxin B1 and dimethylsulfoxide on thymidine-3H uptake and mitosis in rat liver. Cancer Res. 1967 May;27(5):855–864. [PubMed] [Google Scholar]
  20. Swenson D. H., Lin J. K., Miller E. C., Miller J. A. Aflatoxin B1-2,3-oxide as a probable intermediate in the covalent binding of aflatoxins B1 and B2 to rat liver DNA and ribosomal RNA in vivo. Cancer Res. 1977 Jan;37(1):172–181. [PubMed] [Google Scholar]
  21. Swenson D. H., Miller E. C., Miller J. A. Aflatoxin B1-2,3-oxide: evidence for its formation in rat liver in vivo and by human liver microsomes in vitro. Biochem Biophys Res Commun. 1974 Oct 8;60(3):1036–1043. doi: 10.1016/0006-291x(74)90417-3. [DOI] [PubMed] [Google Scholar]
  22. Swenson D. H., Miller J. A., Miller E. C. 2,3-Dihydro-2,3-dihydroxy-aflatoxin B1: an acid hydrolysis product of an RNA-aflatoxin B1 adduct formed by hamster and rat liver microsomes in vitro. Biochem Biophys Res Commun. 1973 Aug 21;53(4):1260–1267. doi: 10.1016/0006-291x(73)90601-3. [DOI] [PubMed] [Google Scholar]
  23. Wogan G. N., Newberne P. M. Dose-response characteristics of aflatoxin B1 carcinogenesis in the rat. Cancer Res. 1967 Dec;27(12):2370–2376. [PubMed] [Google Scholar]
  24. Wong J. J., Hsieh D. P. Mutagenicity of aflatoxins related to their metabolism and carcinogenic potential. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2241–2244. doi: 10.1073/pnas.73.7.2241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. de Recondo A. M., Frayssinet C., Lafarge C., Le Breton E. Action de l'aflatoxine sur le métabolisme du DNA au cours de l'hypertrophie compensatrice du foie après hepatectomie partielle. Biochim Biophys Acta. 1966 May 19;119(2):322–330. [PubMed] [Google Scholar]