N-(2-Hydroxyethyl)-L-valyl-L-leucine in rat urine as a hydrolytic cleavage product of ethylene oxide adduct with globin

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F75010330%3A_____%2F19%3A00012599" target="_blank" >RIV/75010330:_____/19:00012599 - isvavai.cz</a>

Result on the web

<a href="https://link.springer.com/article/10.1007%2Fs00204-019-02388-8" target="_blank" >https://link.springer.com/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>

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

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 mu mol/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 alpha- and beta-chains, respectively. The ratio of HEVL/HEVH (1:3) reflected higher reactivity of EO with the beta-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

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30305 - Occupational health

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)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

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

Name of the periodical

Archives of Toxicology

ISSN

0340-5761

e-ISSN

1432-0738

Volume of the periodical

93

Issue of the periodical within the volume

3

Country of publishing house

DE - GERMANY

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