Induction and repair of DNA cross-links induced by sulfur mustard in the A-549 cell line followed by a comet assay

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F15%3A10319861" target="_blank" >RIV/00179906:_____/15:10319861 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/15:43875393

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.cbi.2015.05.009" target="_blank" >http://dx.doi.org/10.1016/j.cbi.2015.05.009</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cbi.2015.05.009" target="_blank" >10.1016/j.cbi.2015.05.009</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Induction and repair of DNA cross-links induced by sulfur mustard in the A-549 cell line followed by a comet assay

Popis výsledku v původním jazyce

Sulfur mustard is a highly toxic chemical warfare agent with devastating impact on intoxicated tissues. DNA cross-links are probably the most toxic DNA lesions induced in the cell by sulfur mustard. The comet assay is a very sensitive method for measuring DNA damage. In the present study using the A-549 lung cell line, the comet assay protocol was optimized for indirect detection of DNA cross-links induced by sulfur mustard. The method is based on the additional treatment of the assayed cells containing cross-links with the chemical mutagen, styrene oxide. Alkali-labile adducts of styrene oxide cause DNA breaks leading to the formation of comets. A significant dose-dependent reduction of DNA migration of the comet's tail was found after exposing cells to sulfur mustard, indicative of the amount of sulfur mustard induced cross-links. The remarkable decrease of % tail DNA could be observed as early as 5 min following exposure to sulfur mustard and the maximal effect was found after 30 min, when DNA migration was reduced to the minimum. Sulfur mustard preincubated in culture medium without cells lost its ability to induce cross-links and had a half-life of about 15 min. Pre-incubation longer than 30 min does not lead to a significant increase in cross-links when applied to cells. However, the amount of cross-links is decreased during further incubation due to repair. The current modification of the comet assay provides a useful tool for detecting DNA cross-links induced by sulfur mustard and could be used for detection of other DNA cross-linking agents such as chemotherapeutic drugs.

Název v anglickém jazyce

Induction and repair of DNA cross-links induced by sulfur mustard in the A-549 cell line followed by a comet assay

Popis výsledku anglicky

Sulfur mustard is a highly toxic chemical warfare agent with devastating impact on intoxicated tissues. DNA cross-links are probably the most toxic DNA lesions induced in the cell by sulfur mustard. The comet assay is a very sensitive method for measuring DNA damage. In the present study using the A-549 lung cell line, the comet assay protocol was optimized for indirect detection of DNA cross-links induced by sulfur mustard. The method is based on the additional treatment of the assayed cells containing cross-links with the chemical mutagen, styrene oxide. Alkali-labile adducts of styrene oxide cause DNA breaks leading to the formation of comets. A significant dose-dependent reduction of DNA migration of the comet's tail was found after exposing cells to sulfur mustard, indicative of the amount of sulfur mustard induced cross-links. The remarkable decrease of % tail DNA could be observed as early as 5 min following exposure to sulfur mustard and the maximal effect was found after 30 min, when DNA migration was reduced to the minimum. Sulfur mustard preincubated in culture medium without cells lost its ability to induce cross-links and had a half-life of about 15 min. Pre-incubation longer than 30 min does not lead to a significant increase in cross-links when applied to cells. However, the amount of cross-links is decreased during further incubation due to repair. The current modification of the comet assay provides a useful tool for detecting DNA cross-links induced by sulfur mustard and could be used for detection of other DNA cross-linking agents such as chemotherapeutic drugs.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

KA - Vojenství

OECD FORD obor

—

Projekt

<a href="/cs/project/OVUOFVZ200810" target="_blank" >OVUOFVZ200810: YPERIT - Možnosti ovlivnění toxických účinků sirného yperitu</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Chemico-Biological Interactions

ISSN

0009-2797

e-ISSN

—

Svazek periodika

237

Číslo periodika v rámci svazku

July

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

7

Strana od-do

31-37

Kód UT WoS článku

000358268300005

EID výsledku v databázi Scopus

2-s2.0-84929598495