Dosimetry of N6-Formyllysine Adducts Following [13C2H2]-Formaldehyde Exposures in Rats

被引:28
作者
Edrissi, Bahar [1 ]
Taghizadeh, Koli [2 ]
Moeller, Benjamin C. [3 ,4 ]
Kracko, Dean [4 ]
Doyle-Eisele, Melanie [4 ]
Swenberg, James A. [3 ]
Dedon, Peter C. [1 ,2 ]
机构
[1] MIT, Dept Biol Engn, Cambridge, MA 02139 USA
[2] MIT, Ctr Environm Hlth Sci, Cambridge, MA 02139 USA
[3] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27514 USA
[4] Lovelace Resp Res Inst, Albuquerque, NM 87108 USA
关键词
FORMYLATION; PROTEINS; LYSINE;
D O I
10.1021/tx400320u
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
With formaldehyde as the major source of endogenous N-6-formyllysine protein adducts, we quantified endogenous and exogenous N6-formyllysine in the nasal epithelium of rats exposed by inhalation to 0.7, 2, 5.8, and 9.1 ppm [(CH2)-C-15-H-2]-formaldehyde using liquid chromatography-coupled tandem mass spectrometry. Exogenous N-6-formyllysine was detected in the nasal epithelium, with concentration-dependent formation in total as well as fractionated (cytoplasmic, membrane, nuclear) proteins, but was not detected in the lung, liver, or bone marrow. Endogenous adducts dominated at all exposure conditions, with a 6 h 9.1 ppm formaldehyde exposure resulting in one-third of the total load of N-6-formyllysine being derived from exogenous sources. The results parallel previous studies of formaldehyde-induced DNA adducts.
引用
收藏
页码:1421 / 1423
页数:3
相关论文
共 10 条
[1]   Quantitative Analysis of Histone Modifications: Formaldehyde Is a Source of Pathological N6-Formyllysine That Is Refractory to Histone Deacetylases [J].
Edrissi, Bahar ;
Taghizadeh, Koli ;
Dedon, Peter C. .
PLOS GENETICS, 2013, 9 (02)
[2]  
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2012, IARC Monogr Eval Carcinog Risks Hum, V100, P9
[3]   N-formylation of lysine in histone proteins as a secondary modification arising from oxidative DNA damage [J].
Jiang, Tao ;
Zhou, Xinfeng ;
Taghizadeh, Koli ;
Dong, Min ;
Dedon, Peter C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (01) :60-65
[4]   Chromatin modifications and their function [J].
Kouzarides, Tony .
CELL, 2007, 128 (04) :693-705
[5]   Heterochromatin Protein 1 Is Extensively Decorated with Histone Code-like Post-translational Modifications [J].
LeRoy, Gary ;
Weston, John T. ;
Zee, Barry M. ;
Young, Nicolas L. ;
Plazas-Mayorca, Mariana D. ;
Garcia, Benjamin A. .
MOLECULAR & CELLULAR PROTEOMICS, 2009, 8 (11) :2432-2442
[6]   Molecular Dosimetry of N2-Hydroxymethyl-dG DNA Adducts in Rats Exposed to Formaldehyde [J].
Lu, Kun ;
Moeller, Benjamin ;
Doyle-Eisele, Melanie ;
McDonald, Jacob ;
Swenberg, James A. .
CHEMICAL RESEARCH IN TOXICOLOGY, 2011, 24 (02) :159-161
[7]   Formaldehyde Carcinogenicity Research: 30 Years and Counting for Mode of Action, Epidemiology, and Cancer Risk Assessment [J].
Swenberg, James A. ;
Moeller, Benjamin C. ;
Lu, Kun ;
Rager, Julia E. ;
Fry, Rebecca C. ;
Starr, Thomas B. .
TOXICOLOGIC PATHOLOGY, 2013, 41 (02) :181-189
[8]   Peroxynitrite-Induced Nitrative and Oxidative Modifications Alter Tau Filament Formation [J].
Vana, Laurel ;
Kanaan, Nicholas M. ;
Hakala, Kevin ;
Weintraub, Susan T. ;
Binder, Lester I. .
BIOCHEMISTRY, 2011, 50 (07) :1203-1212
[9]   Nε-Formylation of lysine is a widespread post-translational modification of nuclear proteins occurring at residues involved in regulation of chromatin function [J].
Wisniewski, Jacek R. ;
Zougman, Alexandre ;
Mann, Matthias .
NUCLEIC ACIDS RESEARCH, 2008, 36 (02) :570-577
[10]   Formaldehyde and Leukemia: Epidemiology, Potential Mechanisms, and implications for Risk Assessment [J].
Zhang, Luoping ;
Freeman, Laura E. Beane ;
Nakamura, Jun ;
Hecht, Stephen S. ;
Vandenberg, John J. ;
Smith, Martyn T. ;
Sonawane, Babasaheb R. .
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, 2010, 51 (03) :181-191