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Apoptosis for prediction of radiotherapy late toxicity: lymphocyte subset sensitivity and potential effect of TP53 Arg72Pro polymorphism

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We tested apoptosis levels in in vitro irradiated T-lymphocytes from breast cancer (BC) patients with radiotherapy-induced late effects. Previous results reported in the literature were revised. We also examined the effect of TP53 Arg72Pro polymorphism on irradiation-induced apoptosis (IA). Twenty BC patients, ten with fibrosis and/or telangiectasias and ten matched controls with no late reactions, were selected from those receiving radiotherapy between 1993 and 2007. All patients were followed-up at least 6 years after radiotherapy. Using the combination of both CD3 and CD8 antibodies the in vitro IA was measured in CD3, CD8 and CD4 T-lymphocytes, and CD8 natural killer lymphocytes (CD8 NK) by flow cytometry. The TP53 Arg72Pro genotype was determined by sequencing. Patients with late radiotherapy toxicity showed less IA for all T-lymphocytes except for the CD8 NK. CD8 NK showed the highest spontaneous apoptosis and the lowest IA. IA in patients with toxicity appears to be lower than the control patients only in TP53 Arg/Arg patients (P = 0.077). This difference was not present in patients carrying at least one Pro allele (P = 0.8266). Our data indicate that late side effects induced by radiotherapy of BC are associated to low levels of IA. CD8 NK cells have a different response to in vitro irradiation compared to CD8 T-lymphocytes. It would be advisable to distinguish the CD8 NK lymphocytes from the pool of CD8+ lymphocytes in IA assays using CD8+ cells. Our data suggest that the 72Pro TP53 allele may influence the IA of patients with radiotherapy toxicity.

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Acknowledgments

This study was supported by the ‘‘Fondo de Investigación Sanitaria’’ [FIS 05/2181] from the Spanish Health Ministry and the ‘‘Fundación de Investigación Médica Mutua Madrileña’’ [FMMA 2008–2012] grants. Dr Sara Gutiérrez-Enríquez is currently funded by a Miguel Servet contract awarded by the Instituto de Salud Carlos III of the “Ministerio Español de Economía y Competitividad”. We are grateful to the BC donor patients involved in this study.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Radiation Oncology Department, Santa Creu i Sant Pau Hospital, Barcelona, Spain

    María J. Fuentes-Raspall

  2. Clinical Laboratories, University Hospital of Vall d’Hebron, Barcelona, Spain

    Isabel Caragol

  3. Medical Oncology Department, Santa Creu i Sant Pau Hospital, Barcelona, Spain

    Carmen Alonso, Teresa Ramón y Cajal & David Fisas

  4. Medical Physics Department, University Hospital of Vall d’Hebron, Barcelona, Spain

    Alejandro Seoane

  5. Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain

    Nerea Carvajal, Sandra Bonache & Sara Gutiérrez-Enríquez

  6. Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, University Hospital of Vall d’Hebron, Barcelona, Spain

    Orland Díez

  7. Oncogenetics Laboratory, Vall d’Hebron Institute of Oncology (VHIO), Planta 2 Modular Laboratoris Clinics, Hospital of Vall d’Hebron, Pg Vall d’Hebron 119-129, 08035, Barcelona, Spain

    Sara Gutiérrez-Enríquez

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  1. María J. Fuentes-Raspall
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Fuentes-Raspall, M.J., Caragol, I., Alonso, C. et al. Apoptosis for prediction of radiotherapy late toxicity: lymphocyte subset sensitivity and potential effect of TP53 Arg72Pro polymorphism. Apoptosis 20, 371–382 (2015). https://doi.org/10.1007/s10495-014-1056-2

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