Hydrolytic cleavage products of globin adducts in urine as possible biomarkers of cumulative dose: proof of concept using styrene oxide as a model adduct-forming compound

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F75010330%3A_____%2F16%3A00011284" target="_blank" >RIV/75010330:_____/16:00011284 - isvavai.cz</a>

Alternative codes found

RIV/60461373:22310/16:43902187

Result on the web

<a href="http://pubs.acs.org/doi/abs/10.1021/acs.chemrestox.5b00518" target="_blank" >http://pubs.acs.org/doi/abs/10.1021/acs.chemrestox.5b00518</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.chemrestox.5b00518" target="_blank" >10.1021/acs.chemrestox.5b00518</a>

Result language

angličtina

Original language name

Hydrolytic cleavage products of globin adducts in urine as possible biomarkers of cumulative dose: proof of concept using styrene oxide as a model adduct-forming compound

Original language description

A new experimental model was designed to study the fate of globin adducts with styrene 7,8-oxide (SO), a metabolic intermediate of styrene and a model electrophilic compound. Rat erythrocytes were incubated with SO at 7 or 22 -C. Levels of specific amino acid adducts in globin were determined by LC/MS analysis of the globin hydrolysate, and erythrocytes with known adduct content were administered intravenously to recipient rats. The course of adduct elimination from the rat blood was measured over the following 50 days. In the erythrocytes incubated at 22 -C, a rapid decline in the adduct levels on the first day post-transfusion followed by a slow phase of elimination was observed. In contrast, the adduct elimination in erythrocytes incubated at 7 -C was nearly linear, copying elimination of intact erythrocytes. In the urine of recipient rats, regioisomeric SO adducts at cysteine, valine, lysine, and histidine in the form of amino acid adducts and/or their acetylated metabolites as well as SO-dipeptide adducts were identified by LC/MS supported by synthesized reference standards. S-(2-Hydroxy-1-phenylethyl)cysteine and S-(2-hydroxy-2-phenylethyl)cysteine, the most abundant globin adducts, were excreted predominantly in the form of the corresponding urinary mercapturic acids (HPEMAs). Massive elimination of HPEMAs via urine occurred within the first day from the erythrocytes incubated at both 7 and 22 -C. However, erythrocytes incubated at 7 -C also showed a slow second phase of elimination such that HPEMAs were detected in urine up to 50 days post-transfusion. These results indicate for the first time that globin adducts can be cleaved in vivo to modified amino acids and dipeptides. The cleavage products and/or their predictable metabolites are excreted in urine over the whole life span of erythrocytes. Some of the urinary adducts may represent a new type of noninvasive biomarker for exposure to adduct-forming chemicals.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

<a href="/en/project/NT13401" target="_blank" >NT13401: Degradation products of protein adducts in urine as a new type of biomarkers in toxicology</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Chemical Research in Toxicology

ISSN

0893-228X

e-ISSN

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Volume of the periodical

29

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

676-686

UT code for WoS article

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EID of the result in the Scopus database

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