N-(2-Hydroxyethyl)-L-valyl-L-leucine in rat urine as a hydrolytic cleavage product of ethylene oxide adduct with globin cleavage product of ethylene oxide adduct with globin
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F19%3A43918313" target="_blank" >RIV/60461373:22310/19:43918313 - isvavai.cz</a>
Result on the web
<a href="https://link-springer-com.ezproxy.vscht.cz/article/10.1007%2Fs00204-019-02388-8" target="_blank" >https://link-springer-com.ezproxy.vscht.cz/article/10.1007%2Fs00204-019-02388-8</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00204-019-02388-8" target="_blank" >10.1007/s00204-019-02388-8</a>
Alternative languages
Result language
angličtina
Original language name
N-(2-Hydroxyethyl)-L-valyl-L-leucine in rat urine as a hydrolytic cleavage product of ethylene oxide adduct with globin cleavage product of ethylene oxide adduct with globin
Original language description
Ethylene oxide (EO), a genotoxic industrial chemical and sterilant, forms covalent adducts with DNA and also with nucleophilic amino acids in proteins. The adduct with N-terminal valine in globin [N-(2-hydroxyethyl)valine (HEV)] has been used in biomonitoring of cumulative exposures to EO. Here we studied in rats the fate of EO-adducted N-termini of globin after life termination of the erythrocytes. Rat erythrocytes were incubated with EO to produce the HEV levels in globin at 0.4–13.2 μmol/g as determined after acidic hydrolysis. Alternative hydrolysis of the isolated globin with enzyme pronase afforded N-(2-hydroxyethyl)-l-valyl-l-leucine (HEVL) and N-(2-hydroxyethyl)-l-valyl-l-histidine (HEVH), the EO-adducted N-terminal dipeptides of rat globin α- and β-chains, respectively. The ratio of HEVL/HEVH (1:3) reflected higher reactivity of EO with the β-chain. The EO-modified erythrocytes were then given intravenously to the recipient rats. HEVL and HEVH were found to be the ultimate cleavage products excreted in the rat urine. Finally, rats were dosed intraperitoneally with EO, 50 mg/kg. Herein, the initial level of globin-bound HEVL (11.7 ± 1.3 nmol/g) decreased almost linearly over 60 days corresponding to the life span of rat erythrocytes. Daily urinary excretion of HEVL was almost constant for 30–40 days, decreasing faster in the subsequent phase of elimination. Recoveries of the total urinary HEVL from its globin-bound form were 84 ± 6% and 101 ± 17% after administrations of EO and the EO-modified erythrocytes, respectively. In conclusion, urinary HEVL appears to be a promising novel non-invasive biomarker of human exposures to EO.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10406 - Analytical chemistry
Result continuities
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)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Archives of Toxicology
ISSN
0340-5761
e-ISSN
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Volume of the periodical
93
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
603-613
UT code for WoS article
000463730100003
EID of the result in the Scopus database
2-s2.0-85060456949