Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F16%3A00471970" target="_blank" >RIV/68081707:_____/16:00471970 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00216224:14110/16:00087934 RIV/62156489:43210/16:43909576 RIV/61389030:_____/16:00471970
Výsledek na webu
<a href="https://pubs.acs.org/doi/10.1021/acs.jmedchem.5b01628#" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jmedchem.5b01628#</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.5b01628" target="_blank" >10.1021/acs.jmedchem.5b01628</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells
Popis výsledku v původním jazyce
Amifostine protects normal cells from DNA damage induction by ionizing radiation or chemotherapeutics, whereas cancer cells typically remain uninfluenced. While confirming this phenomenon, we have revealed by comet assay and currently the most sensitive method of DNA double strand break (DSB) quantification (based on gamma H2AX/53BP1 high-resolution immunofluorescence microscopy) that amifostine treatment supports DSB repair in gamma-irradiated normal NHDF fibroblasts but alters it in MCF7 carcinoma cells. These effects follow from the significantly lower activity of alkaline phosphatase measured in MCF7 cells and their supernatants as compared with NHDF fibroblasts. Liquid chromatography-mass spectrometry confirmed that the amifostine conversion to WR-1065 was significantly more intensive in normal NHDF cells than in tumor MCF cells. In conclusion, due to common differences between normal and cancer cells in their abilities to convert amifostine to its active metabolite WR-1065, amifostine may not only protect in multiple ways normal cells from radiation-induced DNA damage but also make cancer cells suffer from DSB repair alteration.
Název v anglickém jazyce
Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells
Popis výsledku anglicky
Amifostine protects normal cells from DNA damage induction by ionizing radiation or chemotherapeutics, whereas cancer cells typically remain uninfluenced. While confirming this phenomenon, we have revealed by comet assay and currently the most sensitive method of DNA double strand break (DSB) quantification (based on gamma H2AX/53BP1 high-resolution immunofluorescence microscopy) that amifostine treatment supports DSB repair in gamma-irradiated normal NHDF fibroblasts but alters it in MCF7 carcinoma cells. These effects follow from the significantly lower activity of alkaline phosphatase measured in MCF7 cells and their supernatants as compared with NHDF fibroblasts. Liquid chromatography-mass spectrometry confirmed that the amifostine conversion to WR-1065 was significantly more intensive in normal NHDF cells than in tumor MCF cells. In conclusion, due to common differences between normal and cancer cells in their abilities to convert amifostine to its active metabolite WR-1065, amifostine may not only protect in multiple ways normal cells from radiation-induced DNA damage but also make cancer cells suffer from DSB repair alteration.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30104 - Pharmacology and pharmacy
Návaznosti výsledku
Projekt
—
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2016
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Journal of Medicinal Chemistry
ISSN
0022-2623
e-ISSN
—
Svazek periodika
59
Číslo periodika v rámci svazku
7
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
15
Strana od-do
3003-3017
Kód UT WoS článku
000374430800010
EID výsledku v databázi Scopus
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