Predictive DNA damage signaling for lowdose ionizing radiation.
Int J Mol Med
; 53(6)2024 Jun.
Article
de En
| MEDLINE
| ID: mdl-38695243
ABSTRACT
Numerous studies have attempted to develop biological markers for the response to radiation for broad and straightforward application in the field of radiation. Based on a public database, the present study selected several molecules involved in the DNA damage repair response, cell cycle regulation and cytokine signaling as promising candidates for lowdose radiationsensitive markers. The HuT 78 and IM9 cell lines were irradiated in a concentrationdependent manner, and the expression of these molecules was analyzed using western blot analysis. Notably, the activation of ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (CHK2), p53 and H2A histone family member X (H2AX) significantly increased in a concentrationdependent manner, which was also observed in human peripheral blood mononuclear cells. To determine the radioprotective effects of cinobufagin, as an ATM and CHK2 activator, an in vivo model was employed using sublethal and lethal doses in irradiated mice. Treatment with cinobufagin increased the number of bone marrow cells in sublethal irradiated mice, and slightly elongated the survival of lethally irradiated mice, although the difference was not statistically significant. Therefore, KU60019, BML277, pifithrinα, and nutlin3a were evaluated for their ability to modulate radiationinduced cell death. The use of BML277 led to a decrease in radiationinduced pCHK2 and γH2AX levels and mitigated radiationinduced apoptosis. On the whole, the present study provides a novel approach for developing drug candidates based on the profiling of biological radiationsensitive markers. These markers hold promise for predicting radiation exposure and assessing the associated human risk.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Rayonnement ionisant
/
Altération de l'ADN
/
Transduction du signal
/
Protéines mutées dans l'ataxie-télangiectasie
Limites:
Animals
/
Humans
/
Male
Langue:
En
Journal:
Int J Mol Med
Sujet du journal:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Année:
2024
Type de document:
Article