THE ROLE OF APOPTOSIS IN THYMIC INVOLUTIO N DURING GROWTH OF A SYNGENEIC TRANSPLANTABLE MURINE TUMOR

Thymic involution accompanies the growth of many human and animals tum ors but the precise mechanism of this phenomenon is unknown. We tried to elucidate the role of apoptosis as a possible mechanism of thymic i nvolution during tumor growth. The mice were inoculated subcutaneously with syngeneic hepatoma 22a cells. Starting from the 3rd week after t umor inoculation, progressive thymic involution was observed. Histolog ical studies revealed distinct delymphatization of the thymic cortex, reduced numbers of big lymphocytes in the subcapsular zone and of mito ses in the cortex, and an increased amount of mast cells. This was fol lowed by decreased DNA synthesis in vitro as measured from H-3-thymidi ne incorporation. The number of pycnoses in the cortex was two to thre e times that in the thymus of control animals. DNA gel electrophoresis did not reveal any signs of apoptosis in the thymocytes without prein cubation. Within 2 h of in vitro incubation of the thymocytes taken on the 7th day after the tumor inoculation, spontaneous apoptosis was mo re expressed than in the thymocytes from intact mice. This may reflect different induction mechanisms of apoptosis in the thymocytes from th e tumor bearing and control mice. We propose that the mechanism of thy mic involution during tumor growth is related to inhibition of thymocy tes' proliferation, impaired differentiation and enhanced intrathymic death caused by cytokine release from the nonlymphoid thymic populatio n.