Alterations in the mitochondria of human osteosarcoma cells with glucocorticoids.

acid and protein metabolism in the normal liver tissue. Following i.m. administration of hydrocortisone in mice, electron microscopic examination of the liver was performed from 1 to 48 hr after the injection and an increase in mitochondria in the sections of liver cells was demonstrated. Using morphometric and stereographic techniques combined with statistical analysis, a curve was constructed by these authors, depicting the size and distribution of the nucleus and the mitochondria. In their investigation they found an increase in the size of the mitochondria in hepatocytes but a degeneration of the mitochondria in the thymus cells of mice (8). Whether this thymic mitochondrial degeneration was the result of lymphocytolytic action of cortisone on the thymus or a process of aging is conjectural. In tumors sensitive to cortisone, karyorrhexis has been observed within 24 hr after exposure to glucocorticoids. Rosen et a!. (1 1) postulated that the reduced energy utilization may be of significance in mediating the physiological action of glucocorticoids on cortisone-sensitive lymphosarcoma P1798. On the other hand, cortisone in vivo has been shown to have an anabolic effect on normal mouse liver, which was tentatively postulated as being related to adaptation of enzymes concerned with glucogenesis of amino acids (13). Corticosteroids have been used in the treatment of leukemia and other cancers. The present investigation was undertaken to study the effects of glucocorticoids on human osteosarcoma cells in tissue culture. Since cells in tissue culture do not have any intercellular orientation, all feedback mechanisms at both the organ and intercellular levels were eliminated in this study. MATERIALS AND METHODS M.T. cells from a biologically proven osteosarcoma, which had been cultured and cloned by him and have been subcultured through many passages for the last 5 years, were obtained from Dr. Robert McAllister. An independent colony of these cells has been maintained and subcultured in our laboratory for the last 2.5 years. These cells initially had high levels of alkaline phosphatase activity (10). On prolonged passage through tissue culture, the cells showed minimal, if any, alkaline phosphatase (biochemical marker) activity, either biochemically or by electron microscopy. Biochemical marker activity was inducible in these cells by adding hydrocortisone 21-phosphate, 0.5 jig/mi, to the tissue culture medium. The cells were maintained as a continuous cell line in SUMMARY The effect of glucocorticoids on the mitochondria of human osteosarcoma cells in tissue culture has been investigated by adding hydrocortisone 21-phosphate, 0.5 jig/ml, …