Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 May;80(9):2695–2698. doi: 10.1073/pnas.80.9.2695

Base substitution mutations induced by metabolically activated aflatoxin B1.

P L Foster, E Eisenstadt, J H Miller
PMCID: PMC393894  PMID: 6405385

Abstract

We have determined the base substitutions generated by metabolically activated aflatoxin B1 in the lacI gene of a uvrB- strain of Escherichia coli. By monitoring over 70 different nonsense mutation sites, we show that activated aflatoxin B1 specifically induced GxC leads to TxA transversions. One possible pathway leading to this base change involves depurination at guanine residues. We consider this mechanism of mutagenesis in the light of our other findings that the carcinogens benzo[a]pyrene diol epoxide and N-acetoxyacetylaminofluorene also specifically induce GxC leads to TxA transversions.

Full text

PDF
2695

Selected References

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

  1. Ames B. N., Mccann J., Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res. 1975 Dec;31(6):347–364. doi: 10.1016/0165-1161(75)90046-1. [DOI] [PubMed] [Google Scholar]
  2. Coulondre C., Miller J. H. Genetic studies of the lac repressor. III. Additional correlation of mutational sites with specific amino acid residues. J Mol Biol. 1977 Dec 15;117(3):525–567. doi: 10.1016/0022-2836(77)90056-0. [DOI] [PubMed] [Google Scholar]
  3. Croy R. G., Essigmann J. M., Reinhold V. N., Wogan G. N. Identification of the principal aflatoxin B1-DNA adduct formed in vivo in rat liver. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1745–1749. doi: 10.1073/pnas.75.4.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Croy R. G., Wogan G. N. Temporal patterns of covalent DNA adducts in rat liver after single and multiple doses of aflatoxin B1. Cancer Res. 1981 Jan;41(1):197–203. [PubMed] [Google Scholar]
  5. Drinkwater N. R., Miller E. C., Miller J. A. Estimation of apurinic/apyrimidinic sites and phosphotriesters in deoxyribonucleic acid treated with electrophilic carcinogens and mutagens. Biochemistry. 1980 Oct 28;19(22):5087–5092. doi: 10.1021/bi00563a023. [DOI] [PubMed] [Google Scholar]
  6. Eisenstadt E., Warren A. J., Porter J., Atkins D., Miller J. H. Carcinogenic epoxides of benzo[a]pyrene and cyclopenta[cd]pyrene induce base substitutions via specific transversions. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1945–1949. doi: 10.1073/pnas.79.6.1945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. FREESE E. B. Transitions and transversions induced by depurinating agents. Proc Natl Acad Sci U S A. 1961 Apr 15;47:540–545. doi: 10.1073/pnas.47.4.540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Foster P. L., Eisenstadt E., Cairns J. Random components in mutagenesis. Nature. 1982 Sep 23;299(5881):365–367. doi: 10.1038/299365a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Foster P. L., Eisenstadt E. Distribution and specificity of mutations induced by neocarzinostatin in the lacI gene of Escherichia coli. J Bacteriol. 1983 Jan;153(1):379–383. doi: 10.1128/jb.153.1.379-383.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Groopman J. D., Croy R. G., Wogan G. N. In vitro reactions of aflatoxin B1-adducted DNA. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5445–5449. doi: 10.1073/pnas.78.9.5445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Howard-Flanders P., Boyce R. P., Theriot L. Three loci in Escherichia coli K-12 that control the excision of pyrimidine dimers and certain other mutagen products from DNA. Genetics. 1966 Jun;53(6):1119–1136. doi: 10.1093/genetics/53.6.1119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kadlubar F. F. A transversion mutation hypothesis for chemical carcinogenesis by N2-substitution of guanine in DNA. Chem Biol Interact. 1980 Sep;31(3):255–263. doi: 10.1016/0009-2797(80)90014-9. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Langer P. J., Shanabruch W. G., Walker G. C. Functional organization of plasmid pKM101. J Bacteriol. 1981 Mar;145(3):1310–1316. doi: 10.1128/jb.145.3.1310-1316.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. McCann J., Choi E., Yamasaki E., Ames B. N. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5135–5139. doi: 10.1073/pnas.72.12.5135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McCann J., Spingarn N. E., Kobori J., Ames B. N. Detection of carcinogens as mutagens: bacterial tester strains with R factor plasmids. Proc Natl Acad Sci U S A. 1975 Mar;72(3):979–983. doi: 10.1073/pnas.72.3.979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Miller J. H. Carcinogens induce targeted mutations in Escherichia coli. Cell. 1982 Nov;31(1):5–7. doi: 10.1016/0092-8674(82)90398-1. [DOI] [PubMed] [Google Scholar]
  22. Morrison D. A. Transformation in Escherichia coli: cryogenic preservation of competent cells. J Bacteriol. 1977 Oct;132(1):349–351. doi: 10.1128/jb.132.1.349-351.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Perry K. L., Walker G. C. Identification of plasmid (pKM101)-coded proteins involved in mutagenesis and UV resistance. Nature. 1982 Nov 18;300(5889):278–281. doi: 10.1038/300278a0. [DOI] [PubMed] [Google Scholar]
  24. Reddy E. P., Reynolds R. K., Santos E., Barbacid M. A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature. 1982 Nov 11;300(5888):149–152. doi: 10.1038/300149a0. [DOI] [PubMed] [Google Scholar]
  25. Schaaper R. M., Glickman B. W., Loeb L. A. Role of depurination in mutagenesis by chemical carcinogens. Cancer Res. 1982 Sep;42(9):3480–3485. [PubMed] [Google Scholar]
  26. Schaaper R. M., Kunkel T. A., Loeb L. A. Infidelity of DNA synthesis associated with bypass of apurinic sites. Proc Natl Acad Sci U S A. 1983 Jan;80(2):487–491. doi: 10.1073/pnas.80.2.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schaaper R. M., Loeb L. A. Depurination causes mutations in SOS-induced cells. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1773–1777. doi: 10.1073/pnas.78.3.1773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Shanabruch W. G., Walker G. C. Localization of the plasmid (pKM101) gene(s) involved in recA+lexA+-dependent mutagenesis. Mol Gen Genet. 1980;179(2):289–297. doi: 10.1007/BF00425456. [DOI] [PubMed] [Google Scholar]
  29. Shapiro R. Chemistry of guanine and its biologically significant derivatives. Prog Nucleic Acid Res Mol Biol. 1968;8:73–112. doi: 10.1016/s0079-6603(08)60544-9. [DOI] [PubMed] [Google Scholar]
  30. Strauss B., Rabkin S., Sagher D., Moore P. The role of DNA polymerase in base substitution mutagenesis on non-instructional templates. Biochimie. 1982 Aug-Sep;64(8-9):829–838. doi: 10.1016/s0300-9084(82)80138-7. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Tabin C. J., Bradley S. M., Bargmann C. I., Weinberg R. A., Papageorge A. G., Scolnick E. M., Dhar R., Lowy D. R., Chang E. H. Mechanism of activation of a human oncogene. Nature. 1982 Nov 11;300(5888):143–149. doi: 10.1038/300143a0. [DOI] [PubMed] [Google Scholar]
  33. Taparowsky E., Suard Y., Fasano O., Shimizu K., Goldfarb M., Wigler M. Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature. 1982 Dec 23;300(5894):762–765. doi: 10.1038/300762a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES