Radiation-induced Autophagic Apoptosis of Rat Splenic Lymphocytes.

Abstract

The present investigation was undertaken with the aim of studying the relationship between apoptosis and autophagy through observation of the alternations in splenic lymphocytes after reversible sublethal cell injury. For this purpose, splenic lymphocytes of rats which were irradiated with γ-ray (total 800 rads), were studied by histochemistry and electron microscopy. After γ-ray irradiation, a large number of splenic lymphocytes developed apoptosis which was classified into two types, i. e. classical apoptosis or apoptosis and autophagic apoptosis. Ultra-structurally, classical apoptosis of lymphocyte assumed the aspects characterized by com-paction of nuclear chromatin and formation of cell fragments. 30-40 min after irradiation, classical apoptosis of lymphocytes was observed in spleen, and became most prominent 2-5hr after irradiation. 3-5hr later, most of apoptotic lymphocytes were phago-cytized by macrophages. Autophagic apoptosis was characterized by the formation of numerous autophagic vacuoles (autophagosomes). Early autophagosomes containing identifiable organelles e. g. mitochondria, ribosomes, smooth and rough endoplasmic reticulum were visible 2-24hr after γ-ray irradiation. The autophagosomes that contained multiplied organelles, nuclear fragments and portions of cytoplasm were formed through the enclosing of cisternae of endoplasmic reticulum around damaged organelles. In most of the autophagic apoptotic lymphocytes, their organelles were essentially increased in number. In addition, except that their nuclei were pyknotic, they did not shrink as other apoptotic cells. Thus, we considered the increase of organelles and formation of autophagic vacuoles in the apoptotic splenic lymphocytes was as one of the self-protective reactions against radiation damage. The results showed that part of the apoptotic cells exhibited marked enhancement of autophagic activity. After γ-ray irradiation, distinct organelle changes occurred in autophagic apoptotic lym-phocytes, and the autophagic apoptotic cells themselves perhaps took part in the elimination of apoptotic bodies. These indicated that the classical and the autophagic apoptosis are two types of cell death that assumed different morphological and functional aspects.