الفهرس 
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Abstract
Radiotherapy is a critical therapeutic technique for around half of all cancer patients. Tumor resistance to radiation doses that generate an acceptable level of normal tissue harm is one of the most fundamental difficulties in radiation oncology. Tumor radioresistance leads to disease progression and failure of loco-regional management. Recently, it was discovered that ferroptosis and pyroptosis play a key role in RT-induced cellular death and tumor regression. Thus, targeting ferroptosis and pyroptosis for radiation sensitization could be a potential therapeutic technique (Tan et al., 2021).
The purpose of the study was to compare between the impact of single dose and fractionated doses of ionizing radiation on ferroptosis and pyroptosis as new cell death mechanisms in Ehrlich solid tumor-bearing mice.
This study included 40 Ehrlich solid tumor-bearing mice divided into five groups:
group I: Include 8 untreated Ehrlich solid tumor-bearing mice.
group II: Include 8 Ehrlich solid tumor-bearing mice exposed to a single dose (6Gy) of ionizing radiation.
group III: Include 8 Ehrlich solid tumor-bearing mice exposed to a fractionated dose (6Gyx2) of ionizing radiation.
group IV: Include 8 Ehrlich solid tumor-bearing mice exposed to a fractionated dose (4Gyx3) of ionizing radiation.
group V: Include 8 Ehrlich solid tumor-bearing mice exposed to a fractionated dose (2Gyx4) of ionizing radiation.
Our results showed that:
• There was a significant increase in ACSL4 and PTGS2 genes expression in tumor tissues after exposure to IR at all doses when compared to the untreated control group. (6Gyx2) treated group resulted in the highest ACSL4 expression followed by (4Gyx3) treated group, then (2Gyx4) treated group and the lowest expression of ACSL4 was in the single dose-treated group (6Gy). In the case of PTGS2 expression, the (6Gyx2) treated group also resulted in the highest PTGS2 expression followed by the (4Gyx3) treated group, then the single dose-treated group (6Gy), and finally (2Gyx4) treated group. Indicating that the high dose per fraction regimen induces the expression of ferroptosis markers more than the low dose per fraction regimen.
• MDA level in blood samples of Ehrlich solid tumor-bearing mice was significantly increased after exposure to IR in 6Gy, (6Gyx2), (4Gyx3) treated groups and insignificantly increased in (2Gyx4) treated group when compared to the untreated control group.
• There was a significant increase in serum iron level after exposure to IR at (6Gyx2), (4Gyx3), and (2x4Gy) treated groups and there was an insignificant increase in serum iron level at the single dose-treated group (6Gy) when compared to the untreated control group.
• Reduced glutathione level was significantly reduced after exposure to IR in (6Gyx2), (4Gyx3), and (2Gyx4) treated groups and insignificantly decreased in the single dose-treated group (6Gy) when compared to the untreated control group.
• There was a decrease in GSDMD-CT, IL-1β, and IL-18 protein levels in tumor tissues after exposure to IR at all doses when compared to the untreated control group.