PMID: 9177180Jun 10, 1997Paper

Reaction of aflatoxin B1 exo-8,9-epoxide with DNA: kinetic analysis of covalent binding and DNA-induced hydrolysis

Proceedings of the National Academy of Sciences of the United States of America
W W Johnson, F P Guengerich

Abstract

The exo isomer of aflatoxin B1 (AFB1) 8,9-epoxide appears to be the only product of AFB1 involved in reaction with DNA and reacts with the N7 atom of guanine via an SN2 reaction from an intercalated state. Although the epoxide hydrolyzes rapidly in H2O (0.6 s-1 at 25 degrees C), very high yields of DNA adduct result. Experimental binding data were fit to a model in which the epoxide forms a reversible complex with calf thymus DNA (Kd = 0.43 mg ml-1, or 1.4 mM monomer equivalents) and reacts with guanine with a rate of 35 s-1. Stopped-flow kinetic analysis revealed attenuation of fluorescence in the presence of DNA that was dependent on DNA concentration. Kinetic spectral analysis revealed that this process represents conjugation of epoxide with DNA, with an extrapolated rate maximum of 42 s-1 and half-maximal velocity at a DNA concentration of 1.8 mg ml-1 (5.8 mM monomer equivalents). The rate of hydrolysis of the epoxide was accelerated by calf thymus DNA in the range of pH 6-8, with a larger enhancement at the lower pH (increase of 0.23 s-1 at pH 6.2 with 0.17 mg DNA ml-1). The same rate enhancement effect was observed with poly[dA-dT].poly[dA-dT], in which the epoxide can intercalate but not form significant levels of N7 pur...Continue Reading

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Citations

Jun 6, 2003·Archives of Pharmacal Research·Hea-Soon Shin, Soon-Kyoung Kwon
Dec 5, 2002·Archives of Biochemistry and Biophysics·F Peter Guengerich
Jul 24, 1998·Mutation Research·F P GuengerichS Langouët
Mar 5, 1999·Mutation Research·J S Wang, J D Groopman
Jun 9, 2001·Mutation Research·F P Guengerich
Jul 17, 2007·Chemical Research in Toxicology·Urban BrenJanez Mavri
Jan 27, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Bill D RoebuckThomas R Sutter
Apr 6, 2006·The AAPS Journal·F Peter Guengerich
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·W R KobertzJ M Essigmann
Sep 12, 2015·Immunopharmacology and Immunotoxicology·Min JiangZhengqiang Yu
Feb 8, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xi-Dai LongQiang Xia
Oct 10, 2013·Environmental Toxicology·Leidy Tatiana Díaz DuranJorge Luis Fuentes Lorenzo
Feb 7, 2006·Cancer Letters·Leanne L Bedard, Thomas E Massey
Aug 15, 2012·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Janez Mavri
Nov 15, 2014·Chemical Research in Toxicology·Urban BrenChris Oostenbrink
Jan 26, 2017·PloS One·Ariana AuyeungHoracio Bach
Jun 29, 2005·International Journal of Toxicology·F Peter Guengerich
Apr 19, 2019·Archiv der Pharmazie·Giovanni RibaudoAlessandra Gianoncelli
Jul 19, 2020·Annual Review of Nutrition·William D FiersIliyan D Iliev
Feb 12, 2017·Oncology Reports·Mowaffaq Adam Ahmed AdamDoblin Anak Sandai
Jan 6, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Martin Klvana, Urban Bren
Jan 5, 2000·Physiological Reviews·G J Schroepfer
Jun 2, 2011·Organic & Biomolecular Chemistry·Kunduchi P VijayalakshmiCherumuttathu H Suresh
Oct 2, 2019·International Journal of Environmental Research and Public Health·Noreddine Benkerroum
Aug 7, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ricky A Sharma, Peter B Farmer
May 20, 2020·Journal of Microbiology and Biotechnology·Marie YamadaHiromasa Imaishi
Aug 30, 2008·Journal of Agricultural and Food Chemistry·Katja GalesaJanez Mavri
Feb 9, 2006·Chemical Reviews·F Peter Guengerich

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