Peripheral leukocyte response to oncological radiotherapy: Expression of heat shock proteins

Abstract

Purpose:To study Heat Shock Proteins (HSP) expression in patients subjected to radiotherapy and their potential use as biomarkers for radiation tolerance. An evaluation is also made of whether irradiated volume is critical to the outcome of normal tissue injury using polymorphonuclear neutrophils as biosensors, and whether HSP antibodies (Ab) may be involved in post-radiotherapy disease.

Material and methods:Twelve patients receiving the same total dose of radiotherapy, but in three different volumes, and four healthy volunteers used as controls were analysed. hsp27 and 70i mRNA were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Southern-blot, HSP by flow cytometry, and HSP-Ab by Enzyme-linked Immnoadsorbent Assay (ELISA). The clinical protocol included radiation related toxicity based on clinical and analytical scales.

Results:Radiotherapy caused hsp downregulation, maximum in patients with the largest irradiated volumes, and a decrease in intracellular HSP content. Patients with greatest intraleukocyte HSP levels before treatment suffered more severe radiation morbidity. Patients with endocrine neoplasms presented the highest HSP-Ab titers.

Conclusions:Radiotherapy downregulates hsp27 and 70i, which would enhance radiosensitivity. HSP content prior to treatment is suggested as a prognostic biomarker for radiation tolerance, with circulating leukocytes as biosensors. HSP-Ab may be biomarkers of tumor disease, but do not seem to be involved in the morbidity of acute post-radiotherapy disease, which is closely related to the volumes irradiated.

Keywords:

• Stress proteins
• radiotherapy
• leukocytes
• immunology
• gene expression
• cell biology
• flow cytometry