Comparison of DNA adduct formation by aristolochic acids in various in vitro activation systems by 32P-post-labelling: evidence for reductive activation by peroxidases

Carcinogenesis
H H SchmeiserM Stiborová

Abstract

Aristolochic acid I (AAI) and aristolochic acid II (AAII), the two major components of the carcinogenic plant extract aristolochic acid (AA), are known to be mutagenic and to form DNA adducts in vivo. According to the structures of the major DNA adducts identified in animals and humans, nitroreduction is the crucial pathway in the metabolic activation of these naturally occurring nitroarenes to their ultimate carcinogenic species. Using the nuclease P1-enhanced version of the 32P-post-labelling assay we investigated the formation of DNA adducts by AAI and AAII in different in vitro activation systems in order to determine the most suitable in vitro system mimicking target tissue activation. Although DNA adducts resulting from oxidative activation of AAs have not yet been identified both reductive and oxidative in vitro systems were employed. In vitro incubations were conducted under standardized conditions (0.3 mM AAs; 4 mM dNp as calf thymus DNA) using rat liver microsomes, xanthine oxidase (a mammalian nitroreductase), horseradish peroxidase, lactoperoxidase and chemical reduction by zinc. Enzymatic incubations were performed under aerobic and anaerobic conditions. A combination of two independent chromatographic systems (ion...Continue Reading

Citations

Jan 9, 2007·Journal of the American Society for Mass Spectrometry·Wan ChanZongwei Cai
Dec 16, 2003·Life Sciences·Shufeng ZhouEdmund Jon Deoon Lee
Feb 19, 1999·Mutation Research·C A BielerH H Schmeiser
Feb 19, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Thomas A RosenquistArthur P Grollman
Mar 25, 2011·American Journal of Physiology. Renal Physiology·Thomas A Rosenquist
Aug 5, 2005·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Deirdre O'DonovanKaren Louise Jones
Mar 8, 2005·Drug Metabolism Reviews·Shufeng ZhouYu-Zong Chen
Dec 24, 2002·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Jean-Pierre Cosyns
Mar 3, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Wan ChanZongwei Cai
May 24, 2008·Toxicology in Vitro : an International Journal Published in Association with BIBRA·S HuljicD R Dietrich
Apr 14, 2005·International Journal of Cancer. Journal International Du Cancer·Marie StiborováEva Frei
Sep 12, 2014·Archives of Toxicology·Marie StiborováHeinz H Schmeiser
Apr 10, 2012·Analytical Biochemistry·Victor RomanovArthur P Grollman
Oct 25, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Marie StiborováHeinz H Schmeiser
Sep 15, 2015·Toxicology Research·Byeong Hwa YunRobert J Turesky
Aug 20, 2016·Archives of Toxicology·Marie StiborováHeinz H Schmeiser
Jul 28, 2017·Chemical Research in Toxicology·Nicholas E Geacintov, Suse Broyde
Oct 19, 2017·International Journal of Molecular Sciences·Marie StiborováHeinz H Schmeiser

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