The study of the biological effects of radiation also has revealed an important role for anti fatty acid agents. The intervention of these substances in the physiopathological processes that occur in the organism under the influence of radiation can be considered to be reactional. They correspond to a response of the organism to changes induced by radiation upon the constituents such as fatty acids.

This antagonism is clearly shown in experiments with animals. The administration of sterol preparations not only reduces the size of ulceration in standard skin radiation lesions but also significantly improves the rate of healing. Insaponifiable fraction preparations from human placenta, beef liver, spleen or blood, as well as from butter, produce such favorable effects. (Fig. 92)

If sterols are administered 24 hours after the radium is inserted (or later), the influence upon the dimensions of the ulcer that develops is reduced and is further reduced with increased delay. In some of the animals treated with 1 cc. of a 5% oily solution of the insaponifiable fraction of human placenta in sesame oil for seven days a week, healing with a normal scar was complete within two weeks. Controls, treated with the oil vehicle only, required an average of more than four weeks to heal. Similar effects were obtained with the administration of 1 cc. of a 7% solution of butanol in saline twice a day, beginning with the day of radium application.

The use of small amounts of radiation has, in general, a different effect to that of intensive radiation from this point of view. This can be attributed to the reactive intervention of anti fatty acids. An exaggerated scar forming effect, prolonged fibroblastic reaction, exaggerated connective tissue formation, and vascular sclerosis and thrombosis resulting from endothelial proliferation are all part of this long term response to moderate amounts of radiation. The same effects are produced by anti fatty acid preparations. All the manifestations are opposite to those obtained with high doses of radiation or fatty acids.

From a clinical point of view, the administration of the insaponifiable fraction preparation had a beneficial radiation effect. Even in lesions that had persisted for years, the pain was observed to disappear after a few days with t.i.d. doses as low as 1 cc. of a 5% solution of the insaponifiable fraction of placenta in oil. In several cases, chronic lesions three to five years old healed in only a few months of treatment.

1) The opposite clinical response to high or low doses was frequently observed in the systemic changes in patients receiving X ray therapy. While high doses led to a manifest lowering of the surface tension of urine and an increase of the sulfhydryl index, together with the other changes corresponding to offbalance D for small doses of radiation, certain opposite effects related to a predominance of sterols were noted. Of particular interest was the absence of oxidizing substances in the urine, and the changes in urinary surface tension. In all cases treated, a first reaction to radiation was a higher sulfhydryl index and low surface tension corresponding to a fatty acid predominance. When small or moderate amounts of radiation were used, this reaction was very slight and rapidly disappeared in favor of a second change corresponding to a predominance of sterols with high urinary surface tension, for instance. It is interesting to note at this point that this secondary response has been observed especially in those patients for whom radiation also has had a limited therapeutic effect. As we will see, the dualistic interpretation of data furnished by urinary analysis in patients undergoing radiation therapy can be used to guide this therapy.

Role Of Adrenals

m) The study of the systemic secondary anti fatty acid response to radiation has led to an evaluation of the intervention of the different anti fatty acid agents and to the role of the adrenals. It is known that adrenal hormones have a peculiar effect upon the lymphatic system. They induce a shrinkage of the thymus, spleen, and lymph nodes, along with blood lymphopenia. Since similar effects are produced by irradiation, the problem of the part played by an intervention of these adrenal hormones in the radiation response is of interest.

When the adrenals were removed, shrinkage of the thymus and spleen and lymphopenia still occurred after radiation, but was markedly reduced as compared to nonadrenalectomized irradiated controls. Since shielding of the adrenals during irradiation does not alter the effect upon the lymphocytes and lymphatic organs, the role of the adrenals appears to be an indirect one. Adrenal hormonal secretion appears thus to be a response to the systemic changes induced by irradiation. Adrenalectomy would eliminate this secretion and thereby diminish the degree of lymphopenia and the involution of lymphatic organs. However, the secretion does not result directly as an effect of irradiation of the adrenals since shielding does not influence it. Another factor seems to intervene to stimulate adrenal hormonal secretion. The differences between the effects seen in adrenalec tomized and nonadrenalectomized irradiated animals corresponds thus to the adrenal response to the systemic changes.

In experiments on rats, we have shown that polyunsaturated, and especially conjugated, fatty acids induce changes in the number of lymphocytes a short time after their administration, and that this is followed by involution of the thymus, spleen and lymph nodes. This seems to occur through the intervention of the adrenals since it takes place to a greatly reduced degree when the same amounts of fatty acids are administered to adrenalec tomized animals. The abnormal fatty acids seem to influence the adrenals and their response elicits lymphopenia and involution of lymphatic organs. However, this indirect action through the adrenal glands is only part of the story. Large doses of the same fatty acids will directly induce a certain amount of lymphopenia and involution of the lymphopoedc organs since these changes also occur when these fatty acids are administered in large doses to adrenalectomized animals.

n) All of this research indicates that two of the mechanisms through which radiation acts upon the organism involve changes in lipids. In one, the action is directly through fatty acids; in the other, as a response to these fatty acids, anti fatty acid agents intervene. The role of the adrenals appears to be still more interesting considering the nature of the fatty acids produced by radiation. As seen above, the conjugated trienes appear almost specifically as a result of irradiation of mixtures of fatty acids. It was also seen that the corticoids intervene specifically against these conjugated fatty acids. This correlation seems to represent the link between radiation, conjugated fatty acids and the adrenal response. (Ch. 6, Note 17)