Intrinsic susceptibility to radiation-induced apoptosis of human lymphocyte subpopulations.

ABSTRACT

PURPOSE: With the aim to evaluate intrinsic radiosensitivity, the susceptibility of lymphocyte subpopulations to radiation-induced apoptosis was determined. The investigated parameters included measurement reliability, phenotypic variance, intra- and inter-individual variability, and correlations between radiation-induced and spontaneous apoptosis. METHODS AND MATERIALS Quiescent lymphocytes of 63 healthy volunteers, sampled up to four times over a 1-year period were gamma-irradiated in vitro. Subsequent apoptosis (annexin V) was measured for T4-, T8-, and B-lymphocyte subpopulations using 6-color flow cytometry. Spontaneous apoptosis was measured and radiosensitivity was quantified from the dose-effect curves. RESULTS: After thawing and short-term culture, both spontaneous apoptosis as well as radiation-induced apoptosis (radiosensitivity) differed among the three lymphocyte subpopulations, with T4 being most resistant, and B most sensitive. Spontaneous and radiation-induced apoptosis were correlated in all cell types, and variance between individuals was considerably higher than variance within individuals for both. A small but highly significant increase of both spontaneous and radiation-induced apoptosis was observed with age for T8, but not for T4 and B. Radiosensitivity of T8 and B proved to be sex-independent, whereas female T4 lymphocytes were less radiosensitive than those from males. T4 and T8 radiosensitivities were loosely correlated, and neither of them was related to B radiosensitivity. CONCLUSION: Tendency to spontaneous and radiation-induced apoptosis of lymphocyte subpopulations differs among individuals. In addition, depending on the cell types, age and sex are factors influencing these parameters.