Base and sequence specificities of aflatoxin B1 binding to single- and double-stranded DNAs

Carcinogenesis
F L YuI H Geronimo

Abstract

The inhibitory effect of alfatoxin B1 (AFB1) on the template function for RNA synthesis of several single- and double-stranded DNAs with known base content and sequence was studied in vitro. The results showed that AFB1 strongly inhibits the template function of poly[d(G-C)] and has little, if any, effect on poly[d(A-T)]. Using [3H]AFB1 for the binding, and by spectrum analysis of the appearance of a broad AFB1-DNA adduct peak between 300 and 400 nm right after the typical DNA peak at 260 nm, it is possible to conclude that the binding preference of AFB1 to DNA is: poly[d(G-C)] greater than polydG.polydC greater than polydG greater than polydC, with no detectable binding to poly[d(A-T)]. These studies have therefore provided evidence that the selective inhibition of DNA template function is a direct reflection of the binding specificities of AFB1 to DNA. Furthermore, since there is a 3-fold binding preference of AFB1 for poly[d(G-C)] over polydG.polydC on an equal weight basis, and with very low binding affinity toward either G or C when it is in single-stranded form, these data also suggest: (i) AFB1 binds preferentially to DNA with an alternating G-C sequence compared to DNA with a sequence of contiguous Gs or Cs; and (ii) in...Continue Reading

Citations

May 1, 1994·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·D Kumari, S P Sinha
Jun 1, 1994·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·S Bose, S P Sinha
Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·G Lamm, G R Pack
May 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Maryann E SmelaJohn M Essigmann
Dec 21, 2011·Natural Product Reports·Paris L Hamilton, Dev P Arya

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