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New Study Shows Radiation Increases Iron in Lungs, Offers Insight into Lung Injury

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A new study conducted by a team of researchers from the University of Iowa has shed new light on the long-term impacts of radiation therapy on lung tissues, particularly focusing on the accumulation of iron and the expression of the ferritin heavy chain in the aftermath of radiation exposure. This research offers crucial insights into the mechanisms underlying radiation-induced lung injury (RILI), a significant complication in lung cancer patients undergoing radiation therapy.

The findings were published in the journal Bioengineering.

RILI presents a substantial challenge in clinical settings, affecting a significant number of lung cancer patients. About 77% of lung cancer patients, particularly those with stage I–II non-small-cell lung cancer (NSCLC), are indicated for radiation therapy. However, the sensitivity of lung tissues to radiation can result in RILI, which, in chronic cases, may lead to pulmonary fibrosis, significantly impacting patients’ quality of life.

To delve deeper into the cause of RILI, researchers employed a novel approach using the Small Animal Radiation Research Platform (SARRP). They administered a targeted 20 Gy radiation dose to the right lung of mice while sparing the left lung and heart. This selective approach allowed the study to specifically investigate the effects of radiation on lung tissue while maintaining the left lung as a control.

The study’s findings were significant in revealing a marked increase in iron content and ferritin heavy chain levels in the irradiated lung tissue. Utilising various techniques, including a ferrozine-based assay for quantifying iron accumulation and Western blotting for ferritin heavy chain expression, the research team observed that the irradiated right lungs exhibited elevated levels of iron and ferritin, compared to both sham controls and the unirradiated left lungs. Prussian blue staining of the lung tissues further corroborated these results, visually demonstrating the presence of iron.

These findings are pivotal in understanding the role of iron in lung tissue post-radiation. Iron accumulation in tissues can induce ferroptosis, inflammation, and mitochondrial dysfunction, which are critical factors in the development of RILI. The study’s insights into the correlation between iron levels and ferritin expression open new possibilities for targeted therapies that could mitigate the long-term impacts of radiation therapy, such as the use of ferroptosis inhibitors or iron chelation therapy.

While this study marks a significant advance in our understanding of RILI, it also highlights the need for further research. Given the study’s correlational nature and its limited sample size, more extensive research is essential to fully unravelling the complex mechanisms at play. Additionally, the role of biological factors such as sex in radiation-induced injury, which can influence the susceptibility to fibrosis, warrants further exploration.

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