Description |
The present experiment was designed to investigate a part of the connective tissue steroid metabolism, which is so important to the normal physiological state of an organism. Several conclusions can be drawn from this experiment: 1. The rate of interconversion from Cortisol to cortisone and from cortisone to Cortisol is very different in sarcoma cells than in normal cells. 2. In conversions of Cortisol to cortisone and cortisone to Cortisol, the rate of biotransformation begins more slowly in the malignant cells. Perhaps for some reason Cortisol and cortisone are unable to enter malignant cells as rapidly as normal cells, or the enzymes necessary to the reaction have been incapacitated or inactivated. 3. The conversion to inactive products is much greater in sarcoma cells than in normal cells, so that sarcoma cells seem to squander the biological material necessary to protect the organism against stressors. 4. In the present experiment, conversion to inactive products is greater from cortisone C14 than from Cortisol H3, especially in sarcToma cells. 5. In normal cells, C-11 oxidation is prominent (20 percent at three hours), and it is second only to C-11 reduction which is twice as great (40 percent at three hours). 6. In sarcoma cells, C-11 oxidation is very small (1-3 percent 70 at three hours), so also is C-11 reduction (4 percent at three hours). 7. In normal cells, C-11 reduction is tremendous. This enables normal cells to keep sufficient Cortisol molecules in the active state to protect the animal against stressors and maintain the homeostasis necessary to the normal functioning of the organism. 8. However, sarcoma cells have lost the capacity to convert a large amount of the potentially active cortisone to Cortisol (C-11 reduction). Thus, the amount of Cortisol available is less than in normal cells and control over growth and other processes may be lost. If this applies to the whole animal, peripheral fibroblastic-induced adrenal cortical insufficiency would be produced, leaving less Cortisol present to protect the organism against inflammatory disease and noxious or chemical substances. In this way, the homeostasis so necessary to the normal state is disrupted. If we can discover at what point in normal fibroblast metabolism the capacity of C-11 reduction is lost, we may come closer to the final enigma of the cancer process and thereby have a better chance to control it. But to do this, it is necessary to understand the cell itself and its environment and to understand the metabolism of normal and of malignant cells. By furthering these studies we will be better equipped to develop synthetic hormones and other means which may cause destruction of carcinomatous lesions without being toxic to the organism. |