Effects of X radiation on Lung Cancer Cell Line - The interplay between oxidative stress and P53 levels

Ionizing radiation presents itself in the form of particles (alpha particles, beta particles, protons or neutrons) or electromagnetic radiation (gamma rays and X-rays) with characteristic ionizing power and penetration. Radiotherapy is an essential tool in the treatment of cancer. We can consider various forms of radiation such as external beam radiotherapy, brachytherapy and metabolic radiotherapy. When treating cancer with ionizing radiation all cells within the irradiation volume are more or less exposed. However, if we consider the radiobiology it is expected that normal cells have a higher repair capacity. Considering external beam radiation, the most widely used in the clinics, the total radiation dose administered is generally fractionated being designated by fractionated radiotherapy. When comparing a single shot dose of radiation with fractionated radiotherapy, the benefits regarding recurrence and survival rate appear to be better with the first however radiotoxicity in surrounding normal tissues limits the widespread use.

In the work now published in the journal Medical Oncology, in vitro studies allow us to conclude that ionizing radiation induced a response that adjusts to different cellular injury models, namely linear-quadratic and linear, depending on the molecular characteristics of each cell line, such as the expression of the P53 protein. The preferred type of cell death after exposure to ionizing radiation also shown to be dose and P53 expression profile dependent.

The results published are of utmost importance for the treatment of lung cancer with radiotherapy, since single shot regime was used. In conclusion we can say that molecular and cellular profiles of the different cell lines are crucial to understand the response to ionizing radiation. Consequently also the choice of the cellular injury model should be made taking into account the molecular characteristics of cancer. The integration and implementation of these concepts in clinical practice could contribute to better therapeutic response.

Authors and Affiliations:

Fernando Mendes^1,2,3, Tiago Sales¹, Cátia Domingues^3,4, Susann Schugk¹, Ana Margarida Abrantes^1,3, Ana Cristina Gonçalves^3,4, Ricardo Teixo¹, Rita Silva¹, João Casalta-Lopes^1,5, Clara Rocha^6,7, Mafalda Laranjo¹, Paulo César Simões⁵, Ana Bela Sarmento Ribeiro^3,4,8,9, Maria Filomena Botelho^1,3, Manuel Santos Rosa¹⁰

¹‐ Biophysics Unit - CNC.IBILI, Faculty of Medicine of University of Coimbra, Coimbra, Portugal;

²‐Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Department Biomedical Laboratory Sciences, Coimbra, Portugal;

³-Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine of University of Coimbra, Coimbra, Portugal;

⁴-Applied Molecular Biology and Clinical University of Hematology, Faculty of Medicine of University of Coimbra, Coimbra, Portugal;

⁵-Radiation Oncology Department, Hospital and University Center of Coimbra, Coimbra, Portugal;

⁶ - Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Department Complementary Sciences, Coimbra, Coimbra, Portugal;

⁷-Institute for Systems Engineering and Computers at Coimbra, Coimbra, Portugal,

⁸- Cento Hospitalar Universitário de Coimbra, Coimbra, Portugal;

⁹- CNC.IBILI, Faculty of Medicine, University of Coimbra, Portugal;

¹⁰-Immunology Institute, Faculty of Medicine of University of Coimbra, Coimbra, Portugal.

Abstract:

Lung cancer (LC) ranks as the most prevalent and deadliest cause of cancer death worldwide. Treatment options include surgery, chemotherapy and/or radiotherapy, depending on LC staging, without specific highlight. The aim was to evaluate the effects of X-radiation in three LC cell lines. H69, A549 and H1299 cell lines were cultured and irradiated with 0.5–60 Gy of X-radiation. Cell survival was evaluated by clonogenic assay. Cell death and the role of reactive oxygen species, mitochondrial membrane potential, BAX, BCL-2 and cell cycle were analyzed by flow cytometry. Total and phosphorylated P53 were assessed by western blotting. Ionizing radiation decreases cell proliferation and viability in a dose-, time- and cell line-dependent manner, inducing cell death preferentially by apoptosis with cell cycle arrest. These results may be related to differences in P53 expression and oxidative stress response. The results obtained indicate that sensibility and/or resistance to radiation may be dependent on molecular LC characteristics which could influence response to radiotherapy and treatment success.

Journal: Medical Oncology

Link: http://link.springer.com/article/10.1007%2Fs12032-015-0712-x