Abstract
Objective: Lung is a complex organ with puzzling patterns of radiosensitivity, depending on both the volume and the region of the lung irradiated. In this study, we aimed to investigate stem-like cells distribution in lung lobes and their potential role in regional radiosensitivity and incidences of radiation-induced lung damage (RILD). Methods: Fifteen male Sprague-Dawley rats (8 weeks, 200–250 g) were grouped into two groups: control (sham irradiated, n=6) and treatment (irradiated, n=9). The treatment group received 3 regimens of whole thorax x-ray doses and divided into 3 subgroups: 12 Gy (n=3), 16 Gy (n=3) and 20 Gy (n=3), and monitored for 16 weeks post-radiation. Immunohistochemistry techniques were employed to localize and quantify the distribution of type II pneumocytes, Clara cells and cluster of differentiation (CD) positive stem cells (CD24+, CD44v6+, CD73+), in the upper, middle and lower lobes of the right lung in all rats. Results: The upper lobe was found to harbour more stem-like cells compared to the middle/lower lobes (p < 0.05). The middle and lower lobes contained comparable percentages of different stem-like cells. All stem-like cells tested were distributed unsystematically in the lung tissue with no specific identifiable niches. Conclusion: The upper lobe harbours more population of stem-like cells compared to the lower lobe, this might explain the variation in regional radiosensitivity, with the lower lung lobe being more prone to radiation injury compared to the upper lobe. No specific stem cell niche could be identified in our study. These results may support the development of new-targeted radioprotection strategies to reduce incidences of RILD during radiotherapy.
Highlights
Lung tissue exposure to radiation can occur during the treatment of a variety of cancers such as lung, oesophageal, breast, and various childhood malignancies, leading to increased risk of radiationinduced lung disease (RILD)
The upper lobe of the control non-irradiated lung showed a higher percentage of surfactant B positive cells and Clara cell secretory protein (CCSP) compared to the lower lobe (p=0.024, p=0.014, respectively, Figure 1)
In 12 Gy group, the upper lobe seemed to contain higher percentages of stem-like cells compared to the lower lobe except for CD24 and CD73
Summary
Lung tissue exposure to radiation can occur during the treatment of a variety of cancers such as lung, oesophageal, breast, and various childhood malignancies, leading to increased risk of radiationinduced lung disease (RILD). The mechanisms involved in the initiation and development of RILD remain incompletely understood; many studies have reported a cyclic inflammatory response associated with proinflammatory cytokines [7,8,9]. It is well established from pre-clinical and clinical studies that radiation effects are dependent on the radiation dose and on the volume of lung tissue being exposed to radiation and the region of the lung being irradiated [10,11,12,13,14,15,16]
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