The in vivo formation and repair of DNA adducts from 1′-hydroxysafrole

Author(s):  
David H. Phillips ◽  
Philip C. Hanawalt ◽  
James A. Miller ◽  
Elizabeth C. Miller
Keyword(s):  
Author(s):  
Dirk Steinritz ◽  
Robin Lüling ◽  
Markus Siegert ◽  
Julia Herbert ◽  
Harald Mückter ◽  
...  

AbstractSulfur mustard (SM) is a chemical warfare agent which use is banned under international law and that has been used recently in Northern Iraq and Syria by the so-called Islamic State. SM induces the alkylation of endogenous proteins like albumin and hemoglobin thus forming covalent adducts that are targeted by bioanalytical methods for the verification of systemic poisoning. We herein report a novel biomarker, namely creatine kinase (CK) B-type, suitable as a local biomarker for SM exposure on the skin. Human and rat skin were proven to contain CK B-type by Western blot analysis. Following exposure to SM ex vivo, the CK-adduct was extracted from homogenates by immunomagnetic separation and proteolyzed afterwards. The cysteine residue Cys282 was found to be alkylated by the SM-specific hydroxyethylthioethyl (HETE)-moiety detected as the biomarker tetrapeptide TC(-HETE)PS. A selective and sensitive micro liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry (µLC-ESI MS/HRMS) method was developed to monitor local CK-adducts in an in vivo study with rats percutaneously exposed to SM. CK-adduct formation was compared to already established DNA- and systemic albumin biomarkers. CK- and DNA-adducts were successfully detected in biopsies of exposed rat skin as well as albumin-adducts in plasma. Relative biomarker concentrations make the CK-adduct highly appropriate as a local dermal biomarker. In summary, CK or rather Cys282 in CK B-type was identified as a new, additional dermal target of local SM exposures. To our knowledge, it is also the first time that HETE-albumin adducts, and HETE-DNA adducts were monitored simultaneously in an in vivo animal study.


1980 ◽  
Vol 31 (1) ◽  
pp. 1-17 ◽  
Author(s):  
F.A. Beland ◽  
D.L. Tullis ◽  
F.F. Kadlubar ◽  
K.M. Straub ◽  
F.E. Evans
Keyword(s):  

2009 ◽  
Vol 81 (23) ◽  
pp. 9553-9560 ◽  
Author(s):  
D. García Sar ◽  
M. Montes-Bayón ◽  
E. Blanco González ◽  
L. M. Sierra ◽  
L. Aguado ◽  
...  

1994 ◽  
Vol 15 (11) ◽  
pp. 2553-2558 ◽  
Author(s):  
Henrik Frandsen ◽  
Spiros Grivas ◽  
Robert J. Turesky ◽  
Rolf Andersson ◽  
Lars O. Dragsted ◽  
...  
Keyword(s):  

1985 ◽  
Vol 163 (3) ◽  
pp. 817-823 ◽  
Author(s):  
I Husain ◽  
S G Chaney ◽  
A Sancar
Keyword(s):  

Author(s):  
MARSHALL W. ANDERSON ◽  
PETER I. ADRIAENSSENS ◽  
CATHERINE M. WHITE ◽  
Y. M. IOANNOU ◽  
ALAN G. E. WILSON

1985 ◽  
Vol 62 ◽  
pp. 19-30 ◽  
Author(s):  
F A Beland ◽  
F F Kadlubar
Keyword(s):  

2017 ◽  
Author(s):  
Brian Woo ◽  
Christopher Fang ◽  
Paolo Abada ◽  
Stephen B. Howell ◽  
Olivier Harismendy

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