Immunochemical and proteomic analysis of covalent adducts formed by quinone methide tumor promoters in mouse lung epithelial cell lines

Chemical Research in Toxicology
Brent W MeierJohn A Thompson

Abstract

Two quinone methide (QM) metabolites of the phenolic antioxidant butylated hydroxytoluene (BHT), 2,6-di-tert-butyl-4-methylenecyclohexa-2,5-dienone (BHT-QM) and the tert-butyl-hydroxylated derivative (BHTOH-QM), are believed to be responsible for promoting lung tumor formation in mice treated with BHT. QMs are strongly electrophilic and undergo Michael type additions with nucleophiles at the exocyclic methylene to form benzylic thioether adducts. Our goal was to identify intracellular protein targets of these QMs in order to gain insight into their effects on tumorigenesis. Cell line E10 of mouse lung epithelial origin and its spontaneous transformant, the tumorigenic E9 cell line, were treated with BHT-QM or BHTOH-QM, and cellular proteins were analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Adducted proteins were detected on western blots with polyclonal antibodies developed to a conjugate of BHTOH-QM that recognized adducts of both QMs bound to thiol groups of Cys and side chain amino groups of Lys and His residues. Tryptic digests of immunoreactive proteins were analyzed by HPLC mass spectrometry (LC/MS) and identified by searching protein databases using MS/MS data. In a few cases, ad...Continue Reading

References

Jan 1, 1989·Pharmacology & Therapeutics·H WitschiJ A Thompson
Dec 31, 1997·The Journal of Biological Chemistry·H F Gilbert
Mar 4, 1999·The EMBO Journal·V AdlerZ Ronai
Mar 18, 2004·Journal of Molecular Recognition : JMR·Paulino Gómez-PuertasJosé M Valpuesta

❮ Previous
Next ❯

Citations

Mar 27, 2007·Chemical Research in Toxicology·Tao JiRobert P Hanzlik
Mar 3, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Matthew T LabenskiSerrine S Lau
Mar 21, 2007·BMC Bioinformatics·Robert P HanzlikJianwen Fang
May 4, 2010·Environmental Health Perspectives·Christina DeStefano-ShieldsAlan Buckpitt
Mar 8, 2013·Chemical Research in Toxicology·Yakov M KoenRobert P Hanzlik
Apr 6, 2012·Neurochemical Research·Han-Chang HuangZhao-Feng Jiang
Oct 31, 2008·Proteomics·Ingrid MillerElisabetta Gianazza
Apr 1, 2010·International Journal of Experimental Pathology·Justin M M CatesPampee P Young
Oct 1, 2008·Chemico-biological Interactions·Robert P HanzlikYakov M Koen
May 5, 2007·Molecular Carcinogenesis·Katherine A PeeblesAlvin M Malkinson
Jul 28, 2020·Redox Biology·Álvaro Viedma-PoyatosDolores Pérez-Sala
Nov 6, 2020·Chemical Research in Toxicology·Shane R Byrne, Steven E Rokita
Dec 7, 2007·Chemical Research in Toxicology·Daniel C Liebler
Jun 5, 2014·Chemical Research in Toxicology·Michael P McCraneSteven E Rokita
Mar 19, 2019·Chemical Research in Toxicology·Shane R ByrneSteven E Rokita
Dec 19, 2016·Chemical Research in Toxicology·Jinping GanW Griffith Humphreys

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.