Abstract
AFLATOXIN B1 (AFB1) has the highest biological activity of the four naturally occurring aflatoxins produced by the mould Aspergillus flavus1. Feeding studies have shown it to be the most potent liver carcinogen known for the rat2. Its ingestion by man is associated with the high primary liver cancer incidence in certain parts of Africa3. There is much evidence to suggest that AFB1 requires metabolism to exert both its carcinogenic and mutagenic effects (reviewed in ref. 4). Structure-activity5, as well as chemical studies6,7 indicate that the major route for activation proceeds through mixed function oxidase attack yielding the 8,9-oxide (previously called the 2,3-oxide but renumbered according to IUPAC recommendations). Attempts to chemically synthesise this metabolite have so far been unsuccessful. We report here that peracid oxidation of AFB1 generates AFB1-8,9-oxide, and that this latter compound reacts readily with nucleic acids to give adducts identical to those obtained after liver mixed function oxidase (MFO) activation in vitro and in vivo.
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References
Wogan, G. N. in Methods in Cancer Research (ed. Busch, H.) 309–344 (Academic, New York,1973).
Wogan, G. N., Paglialunga, S. & Newberne, P. M., Fd. Cosmet. Toxicol. 12, 681–685 (1974).
Peers, F. G., Gilman, G. A. & Linsell, C. A., Int. J. Cancer 17, 167–176 (1976).
Campbell, T. C. & Hayes, J. R., Toxicol. appl. Pharm. 35, 199–222 (1976).
Garner, R. C., Miller, E. C. & Miller, J. A., Cancer Res. 32, 2058–2066 (1972).
Swenson, D. H., Miller, E. C. & Miller, J. A., Biochem. biophys. Res. Commun. 60, 1036–1043 (1974).
Garner, R. C., FEBS Lett. 36, 261–264 (1973).
Anderson, W. K. & Veysoglu, T., J. Org. Chem. 38, 2267–2268 (1973).
Miller, C. T., Lawley, P. D. & Shah, S. A., Biochem. J. 136, 387–393 (1973).
Lawley, P. D. & Thatcher, C. A., Biochem. J. 116, 693–707 (1970).
Lawley, P. D. & Brookes, P., Biochem. J. 89, 127–138 (1963).
Lawley, P. D. & Shah, S. A., Chem.-Biol. Interact. 7, 115–120 (1973).
Swenson, D. H., Lin, J. K., Miller, E. C. & Miller, J. A., Cancer Res. 37, 172–181 (1977).
Garner, R. C., Chem.-Biol. Interact. 6, 125–129 (1973).
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The erratum article can be found online at https://doi.org/10.1038/269450d0
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MARTIN, C., GARNER, R. Aflatoxin B-oxide generated by chemical or enzymic oxidation of aflatoxin B1 causes guanine substitution in nucleic acids. Nature 267, 863–865 (1977). https://doi.org/10.1038/267863a0
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DOI: https://doi.org/10.1038/267863a0
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