Identification and Quantification of Aflatoxin Guanine and FapyGuanine Adducts in Mouse Liver invivo by LC-MS/MS Isotope Dilution

Published

March 11, 2018

Author(s)

Erdem Coskun, Vladimir Vartanian, Irina G. Minko, Onur Erdem, Pawel Jaruga, Patricia Egner, John D. Groopman

Abstract

Dietary exposures to aflatoxin contaminated food is one of the major contributions to human hepatocellular carcinomas (HCCs) which accounts for over 700.000 deaths per year, especially in highly populated developing and underdeveloped countries. Aflatoxin B1 (AFB1), among others of the aflatoxin family, is the most carcinogenic and hazardous mycotoxin to animals and humans. Although it is well known that subsequent DNA adduct formation is the most significant mechanism, genetic variants that increase individual susceptibility to AFB1-induced HCCs are poorly understood. Therefore, especially in-vivo studies focusing on the underlying mechanisms of AFB1- induced HCCs followed by the AFB1 exposure have tremendous importance. The primary DNA adduct of AFB1 is AFB1-N7-Gua, which is converted naturally to two secondary lesions, an apurinic site and an AFB1-formamidopyrimidine adduct (AFB1-N7-FapyGua). The AFB1-N7-FapyGua is more mutagenic than the AFB1-N7-Gua, leading to G → T transversions attributed to be the cause of HCCs. The development of successful intervention strategies should be hastened using aflatoxin biomarkers that efficiently assess their efficacy in individuals. Chemical specific biomarkers have been developed in response to the difficulties of traditional metrics of analysis to assess the exposure status and disease risk of individuals. In this context, evolving methods for the sensitive and specific detection of aflatoxin biomarkers are providing important tools for identifying individuals at high risk for disease from dietary exposure to aflatoxins. In this work, we developed a methodology to identify and quantify AFB1-N7-Gua and AFB1-N7-FapyGua in liver of mice treated with AFB1. DNA was isolated from the liver of the control mice and AFB1- treated mice. We used LC-MS/MS with isotope dilution to detect AFB1-N7-Gua, and cis-AFB1-N7- FapyGua and trans-AFB1-N7-FapyGua in isolated DNA samples................ ................................. ..........

Proceedings Title

The Toxicologist

Conference Dates

March 11-15, 2018

Conference Location

San Antonio, TX

Conference Title

57th SOT Annual Meeting and ToxExpo

Pub Type

Conferences

Keywords

Aflatoxins, DNA adducts, LC-MS/MS

Citation

Coskun, E. , Vartanian, V. , Minko, I. , Erdem, O. , Jaruga, P. , Egner, P. and Groopman, J. (2018), Identification and Quantification of Aflatoxin Guanine and FapyGuanine Adducts in Mouse Liver invivo by LC-MS/MS Isotope Dilution, The Toxicologist, San Antonio, TX (Accessed November 21, 2024)