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Aflatoxin B1: Correlations of Patterns of Metabolism and DNA Modification with Biological Effects

  • Robert G. Croy
  • John M. Essigmann
  • Gerald N. Wogan
Part of the Basic Life Sciences book series

Abstract

The molecular mechanisms by which aflatoxin B1 (AFB1) produces its biological effects are poorly understood. Many of the biochemical effects of the aflatoxins and other chemical carcinogens are mediated by activation through metabolism by one or more of the mixed-function oxidases and subsequent covalent modification of cellular macromolecules (1). Experimental evidence indicates that AFB1-2,3-oxide is the ultimate reactive metabolite (2,3). It is reasonable that the sites and amount of macromolecular damage play essential roles determining molecular alterations and consequently observable biological effects. The consequences of covalent damage once formed will depend upon the ability of a cell or tissue to repair (correctly or incorrectly) or circumvent damage to essential cellular components before they are lethal or result in permanent change in the molecular program of the cell. For example, cells from patients with xeroderma pigmentosum that are defective in excision repair have increased sensitivity to ultraviolet (UV) light and some chemical agents. Conversely, cells competent for repair that are given adequate time to remove lesions from DNA before critical events exhibit increased survival (4). Thus, the kinetics of formation of this macromolecular damage and its repair are important. We have studied the covalent products formed in DNA of species sensitive and resistant to the biological effects of AFB1 for correlations that may exist between the formation of these products, their removal, and biological responses to their presence.

Keywords

High Pressure Liquid Chromatography Covalent Product Macromolecular Damage Trout Embryo Rainbow Trout Embryo 
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.

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Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Robert G. Croy
    • 1
  • John M. Essigmann
    • 2
  • Gerald N. Wogan
    • 2
  1. 1.Sidney Farber Cancer InstituteBostonUSA
  2. 2.Department of Nutrition and Food ScienceMassachusetts Institute of TechnologyCambridgeUSA

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