Effect of the inducers of cellular differentiation and of ionizing radiation on thymus lymphocytes: chromatin degradation and programmed cell death.

The cytotoxic response of thymocytes to chemical inducers of differentiation does not represent a non-specific toxic action of these drugs. The death of thymocytes treated with the inducers or with gamma-rays is associated with internucleosomal chromatin fragmentation. All treatments are more effective on the most radiosensitive sub-population of these cells. This subpopulation is characterized by the maximal level of spontaneous DNA lesions. Incubation of thymocytes with the inducers of differentiation raises the level of these lesions. It is suggested that the processes of thymocyte death after the inducer treatment or irradiation and of cellular differentiation have features in common, and the capacity of thymocytes to limit or reverse the potentially lethal effects of these treatments is determined by the level of pre-existing spontaneous DNA lesions.