TY - JOUR
T1 - Apoptosis for prediction of radiotherapy late toxicity: Lymphocyte subset sensitivity and potential effect of TP53 Arg72Pro polymorphism
AU - Fuentes-Raspall, María J.
AU - Caragol, Isabel
AU - Alonso, Carmen
AU - Ramón Y Cajal, Teresa
AU - Fisas, David
AU - Seoane, Alejandro
AU - Carvajal, Nerea
AU - Bonache, Sandra
AU - Díez, Orland
AU - Gutiérrez-Enríquez, Sara
PY - 2015/1/1
Y1 - 2015/1/1
N2 - © 2014 Springer Science+Business Media New York. 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.
AB - © 2014 Springer Science+Business Media New York. 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.
KW - In vitro irradiation-induced apoptosis
KW - Natural killer CD8+ lymphocytes
KW - Radiotherapy-induced late toxicity
KW - T-lymphocytes
KW - TP53 Arg72Pro polymorphism
U2 - 10.1007/s10495-014-1056-2
DO - 10.1007/s10495-014-1056-2
M3 - Article
SN - 1360-8185
VL - 20
SP - 371
EP - 382
JO - Apoptosis
JF - Apoptosis
IS - 3
ER -