7-glutathione pyrrole adduct: a potential DNA reactive metabolite of pyrrolizidine alkaloids

Chemical Research in Toxicology
Qingsu XiaPeter P Fu

Abstract

Pyrrolizidine alkaloid (PA)-containing plants are the most common poisonous plants affecting livestock, wildlife, and humans. PAs require metabolic activation to form pyrrolic metabolites to exert cytotoxicity and tumorigenicity. We previously determined that metabolism of tumorigenic PAs produced four DNA adducts, designated as DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, that are responsible for liver tumor initiation. 7-Glutathione-(±)-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine (7-GS-DHP), formed in vivo and in vitro, and 7,9-di-GS-DHP, formed in vitro, are both considered detoxified metabolites. However, in this study we determined that incubation of 7-GS-DHP with 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) yields DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts as well as the reactive metabolite DHP. Furthermore, reaction of 7-GS-DHP with calf thymus DNA in aqueous solution at 37 °C for 4, 8, 16, 24, 48, or 72 h, followed by enzymatic hydrolysis yielded DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts. Under our current experimental conditions, DHP-dA-3 and DHP-dA-4 adducts were formed in a trace amount from the reaction of 7,9-di-GS-DHP with dA. No DHP-dG-3 or DHP-dG-4 adducts were detected from the reaction of 7...Continue Reading

References

Jun 1, 1976·Chemico-biological Interactions·I N White
Nov 1, 1992·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R L ReedD R Buhler
Jan 1, 1991·Toxicon : Official Journal of the International Society on Toxinology·A R MattocksR J Huxtable
Jan 1, 1991·Advances in Experimental Medicine and Biology·D R BuhlerR L Reed
Nov 1, 1995·Carcinogenesis·H Y KimR A Coulombe
May 1, 1995·Toxicon : Official Journal of the International Society on Toxinology·C C Yan, R J Huxtable
Sep 9, 1999·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·H Y KimR A Coulombe
Aug 4, 2012·Chemical Research in Toxicology·Yuewei ZhaoPeter P Fu

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Citations

Jan 27, 2016·Chemical Research in Toxicology·Weiwei LiJiang Zheng
Jan 14, 2016·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Xiaobo HePeter P Fu
Sep 17, 2015·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·Bart Huybrechts, Alfons Callebaut
Jun 23, 2016·Nutrition Reviews·Lieselot Y Hemeryck, Lynn Vanhaecke
Apr 19, 2017·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Xiaobo HePeter P Fu
Oct 27, 2016·Natural Product Reports·Jeremy Robertson, Kiri Stevens
Oct 4, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Verena SchöningJürgen Drewe
Jun 7, 2019·Drug Metabolism Reviews·S Cyrus KhojastehDonglu Zhang
Oct 30, 2019·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Shruti BudhaniHua Deng
Jul 7, 2018·Journal of Food and Drug Analysis·Jiang MaGe Lin
Sep 16, 2017·Journal of Food and Drug Analysis·Xiaobo HePeter P Fu
Jun 6, 2020·Journal of Environmental Science and Health. Part C, Toxicology and Carcinogenesis·Xiaobo HePeter P Fu
Aug 27, 2019·Drug Metabolism Reviews·Bo Wen, Peter Gorycki
Oct 27, 2018·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Xiaobo HePeter P Fu
Mar 16, 2021·Chemical Research in Toxicology·Ina GeburekDieter Schrenk
May 19, 2021·Archives of Toxicology·Yisheng HeGe Lin
May 11, 2018·Chemical Research in Toxicology·Alf Claesson, Alexander Minidis

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