Radiation-induced DNA damage and repair in human γδ and αβ T-lymphocytes analysed by the alkaline comet assay

Human peripheral blood mononuclear cells (PBMC) are used as surrogate tissue for the assessment of individual sensitivity to ionising radiation [1]. Using the G2 chromosomal aberration assay it has been shown by a number of authors that the radiosensitivity of PBMC is higher in cancer patients compared to healthy donors [2-9]. A similar result was reported using the micronucleus assay [10] and the comet assay [11,12] and is generally interpreted as a reflection of genomic instability in PBMC of cancer patients [10].PBMC are composed of different cell subpopulations which are differently radiosensitive. It is generally accepted that B lymphocytes show a higher radiosensitivity than T-lymphocytes that are all CD3+ [13-16]. Among the T-lymphocytes cytotoxic CD8+ cells appear somewhat more sensitive than helper CD4+ cells [16,17], although this was not observed in all studies [18]. A lymphocyte subpopulation which recently attracted interest is composed of T-lymphocytes with γδ T-cell receptors (TCR). The reason for this is the discovery that these cells contribute to immunity against cancer [19]. In peripheral blood γδ lymphocytes account for less than 5% of total T-lymphocytes while their proportion in the intestine can be much higher [20].Given their role in immunosurveillance, the level and/or the activity of γδ T-lymphocytes is expected to be low in PBMC of cancer-prone individuals and high in PBMC of individuals who are resistant to cancer. This is supported by findings in patients with lymphoma, myeloma, breast and nasopharyngeal carcinoma [21-23]. Should the sensitivity to radiation of γδ lymphocytes be lower than that of the more common αβ T-lymphocytes, this could, at least partly explain the low radiosensitivity of PBMC from healthy individuals compared to cancer patients. The present investigation was carried out to test if there are differences in the radiation sensitivity between different TCR subtype populations by comparing the level of DNA damage and th