Radiation therapy affects YAP expression and intracellular localization by modulating lamin A/C levels in breast cancer

The microenvironment of breast cancer actively participates in tumorigenesis and cancer progression. The changes observed in the architecture of the extracellular matrix initiate an oncogene-mediated cell reprogramming, that leads to a massive triggering of YAP nuclear entry, and, therefore, to cancer cell proliferation, invasion and probably to increased radiation-resistance. However, it is not yet fully understood how radiotherapy regulates the expression and subcellular localization of YAP in breast cancer cells experiencing different microenvironmental stiffnesses. To elucidate the role of extracellular matrix stiffness and ionizing radiations on YAP regulation, we explored the behaviour of two different mammary cell lines, a normal epithelial cell line (MCF10A) and a highly aggressive and invasive adenocarcinoma cell line (MDA-MB-231) interacting with polyacrylamide substrates mimicking the mechanics of both normal and tumour tissues (~1 and ~13 kPa). We report that X-ray radiation affected in a significant way the levels of YAP expression, density, and localization in both cell lines. After 24 h, MCF10A and MDA-MB231 increased the expression level of YAP in both nucleus and cytoplasm in a dose dependent manner and particularly on the stiffer substrates. After 72 h, MCF10A reduced mostly the YAP expression in the cytoplasm, whereas it remained high in the nucleus of cells on stiffer substrates. Tumour cells continued to exhibit higher levels of YAP expression, especially in the cytoplasmic compartment, as indicated by the reduction of nuclear/ cytoplasmic ratio of total YAP. Then, we investigated the existence of a correlation between YAP localization and the expression of the nuclear envelope protein lamin A/C, considering its key role in modulating nuclear deformability and changes in YAP shuttling phenomena. As supposed, we found that the effects of radiation on YAP nucleus/cytoplasmic expression ratio, increasing in healthy cells and decreasing in tumour ones, were accompanied by lower and higher lamin A/C levels in MCF10A and MDAMB-231 cells, respectively. These findings point to obtain a deeper knowledge of the role of the extracellular matrix and the effects of X-rays on YAP and lamin A/C expression that can be used in the design of doses and timing of radiation therapy

Sassi of Matera Building Material: High-Resolution Gamma-Ray Spectroscopy Characterization for Radioprotection

The Sassi of Matera (Basilicata region, southern Italy) is a peculiar site, but not unique in Italy, from a landscape point of view. Most of the buildings are excavated in rocks of calcarenite origin and used as homes and accommodation facilities. For this reason, the contribution of gamma radiation to the population due to this building material has been investigated for the first time. Even though the type of rock is not mentioned among the construction materials indicated in Italian Legislative Decree 101/2020 to be subjected to radiological characterization, the methodology indicated in the decree was applied, comparing the values with those present in the literature. The content of 226Ra, 232Th and 40K was then investigated with gamma spectroscopy, and the gamma index was calculated. The results obtained showed a low level of activity concentration of natural radionuclides in this type of stone, confirming the radiological safety. This result can also support the recovery and restoration initiatives for these buildings to conserve the architectural and landscape heritage of this village

Cytoskeleton Response to Ionizing Radiation: A Brief Review on Adhesion and Migration Effects

The cytoskeleton is involved in several biological processes, including adhesion, motility, and intracellular transport. Alterations in the cytoskeletal components (actin filaments, intermediate filaments, and microtubules) are strictly correlated to several diseases, such as cancer. Furthermore, alterations in the cytoskeletal structure can lead to anomalies in cells’ properties and increase their invasiveness. This review aims to analyse several studies which have examined the alteration of the cell cytoskeleton induced by ionizing radiations. In particular, the radiation effects on the actin cytoskeleton, cell adhesion, and migration have been considered to gain a deeper knowledge of the biophysical properties of the cell. In fact, the results found in the analysed works can not only aid in developing new diagnostic tools but also improve the current cancer treatments

Measurement of Natural Radionuclides in Drinking Water and Risk Assessment in a Volcanic Region of Italy, Campania

The physical–chemical properties of water are closely linked to the geological nature of the site where they are located. This aspect becomes even more interesting when analyzing the natural radionuclides in the drinking water of a volcanic territory such as Campania in southern Italy. This study concerned the measurement of activity concentration of gross alpha and beta, radon, and tritium to evaluate their biological impact. The measurements were carried out using alpha spectrometry for alpha emitters, proportional counter for beta emitters, the electret system for radon in water, and finally liquid scintillation for the measurement of tritium concentration. The biological impact was assessed considering the indicative dose, if applicable, and the effective annual dose of radon. Although the results show that the values are below international and national references, the radiological characterization of drinking water is of fundamental importance to optimize the radiation protection of the population

Adhesion and Migration Response to Radiation Therapy of Mammary Epithelial and Adenocarcinoma Cells Interacting with Different Stiffness Substrates

The structural and mechanical properties of the microenvironmental context have a profound impact on cancer cell motility, tumor invasion, and metastasis formation. In fact, cells react to their mechanical environment modulating their adhesion, cytoskeleton organization, changes of shape, and, consequently, the dynamics of their motility. In order to elucidate the role of extracellular matrix stiffness as a driving force in cancer cell motility/invasion and the effects of ionizing radiations on these processes, we evaluated adhesion and migration as biophysical properties of two different mammary cell lines, over a range of pathophysiological stiffness (1–13 kPa) in a control condition and after the exposure to two different X-ray doses (2 and 10 Gy, photon beams). We concluded that the microenvironment mimicking the normal mechanics of healthy tissue has a radioprotective role on both cell lines, preventing cell motility and invasion. Supraphysiological extracellular matrix stiffness promoted tumor cell motility instead, but also had a normalizing effect on the response to radiation of tumor cells, lowering their migratory capability. This work lays the foundation for exploiting the extracellular matrix-mediated mechanism underlying the response of healthy and tumor cells to radiation treatments and opens new frontiers in the diagnostic and therapeutic use of radiotherapy

COVID-19 and the Additional Radiological Risk during the Lockdown Period in the Province of Naples City (South Italy)

The lockdown restrictions, as a first solution to contain the spread of the COVID-19 pandemic, have affected everyone’s life and habits, including the time spent at home. The latter factor has drawn attention to indoor air quality and the impact on human health, particularly for chemical pollutants. This study investigated how the increasing time indoor influenced exposure to natural radioactive substances, such as radon gas. To calculate the radiological risk, we considered the most consolidated indices used for radiation protection: annual effective dose, excess lifetime cancer risk, and the lung cancer case. Furthermore, two different exposure times were considered: pre-lockdown and post-lockdown. The lockdown increased the indoor exposure time by 4% and, consequently, the radiological risk factors by 9%. Furthermore, the reference value of 300 Bq/m3, considered acceptable for human radiation protection, may need to be lowered further in the case of conditions similar to those of the lockdown period