Louis H. Jorstad

Further Studies of the Effect of Graded Doses of X-rays on Animals Fed on Various Dietaries, with a Note on the Effect of Dietary in the Treatment of Patients with X-Rays

IN previous papers (1) (2) (3) we have described studies of the effect of small repeated and larger repeated doses of X-rays on rats. In these earlier experiments we studied the effect of doses ranging between 10 milliampere minutes2 (13 e-units) and 50 milliampere minutes (68 e-units) given twice a week to rats fed on a balanced dietary and other rats fed on diets deficient in Vitamins A and B, respectively. In these experiments we showed that doses of 13 e-units given twice a week protect for a considerable time rats fed on a diet deficient in Vitamin B, while they have little effect on rats fed on a diet deficient in Vitamin A. Larger doses of 34 and 68 e-units, respectively, given twice a week, protect for a considerable time not only rats fed on a diet deficient in Vitamin B, but also those fed on a diet deficient in Vitamin A. Previous observations on X-rays have shown that they may cause changes in the ionization of atoms; such changes may cause either synthesis in one case or a breakdown of molecu...

Comparative Studies of Histological Skin Changes Produced by X-Rays and by Lipoid Solvents

By varying the time period of exposure and transmitting the ray through an opening 1 cm. in diameter, we have produced various degrees of x-ray burns of the skin in a series of white rats. The quantity of x-rays used varied from 5 miliampere minutes to 50 miliampere minutes. Animals were placed on high vitamin A, low vitamin A, and balanced stock rations to determine if these dietaries would produce a difference in reaction to the x-rays. Our studies, thus far, have not shown any striking differences. The characteristic gross picture is depilation over the area of skin exposed, with the persistence of a roughened, scarred skin that appears from 14 to 21 days after the exposure to the x-rays. Five miliampere minutes and 10 miliampere minutes produce no effect grossly apparent. Microscopically the lesion is that of shrinking and edema of the epithelial layer, hyperplasia of the hair follicles, and in some cases a metaplasia of the basal layer of the skin. The subcutis shows varying degrees of hyalinization. With the high doses (50 miliampere minutes) there is a hyalinization of the subcutis and the glandular structures in it. The epithelium remains intact over the area, the higher dosages producing a pyknosis of the cell nuclei and a hyalinization of the cytoplasm. In the second series we applied a 50 per cent coal tar or pine tar preparation to a denuded area 2 cm. in diameter. The white rat was used. The tar was painted on the area with a cotton swab every 2 or 3 days. A roughening of the skin and a gradual loss of hair was noted grossly. Microscopically a hyperkeratosis begins at the 30th day, and gradually progresses.

The Chemical and Biological Changes Induced by X-rays in Body Tissues1

THE object of a series of experiments which we have been carrying on during the last several years has been to throw light on the general biological action of X-rays. While much work has been done on the immediate effects of these rays on cells of various kinds, little has been learned about the chemical effects induced by them in the organism. One striking fact that has been the outcome of the general studies of X-rays and which promises an eventual solution of this problem when more has been learned about cellular growth in the organism and cancer, is that X-rays are not only able to destroy cancer cells, but may induce cancer. Another equally important fact is that growing cells are more sensitive to these rays than the more differentiated tissue. In the light of these various facts it has become evident, therefore, that X-rays will be understood only when we understand cancer, and every advance in the knowledge of cancer must throw further light upon the nature of the action of these rays. As early as...

The Relation of Dietary to the Effects of Large Amounts of X-rays on the Organism1

IN EARLIER work dating from 1926, we devised a means whereby we could . determine through biological tests on animals the nature of the action of graded doses of X-ray energy on the organism (1). We noted early in this work that the initial dose of X-ray energy produced a gastro-intestinal disturbance in animals, very similar to the gastro-intestinal disturbances which we obtained by the addition of increased quantities of Vitamin B to the organism. In work preceding this we had demonstrated that the Bacterium, tumefaciens in the early culture produced Vitamin B when grown in potato decoction (2). Rats given a ration deficient in Vitamin B showed no signs of Vitamin B deficiency when the early culture of Bacterium tumefaciens was added to the ration; neither did they show toxic symptoms. The weight curves of these animals corresponded to the weight curves of animals which were given relatively small dosages of X-rays (3). When the Bacterium tumefaciens is allowed to overgrow the medium in which it has bee...

The Action of X-Rays on the Organism.

X-rays can produce cancer as well as destroy it. The action of X-rays, therefore, will be understood only when we have first understood the mechanism of growth in tissue cells. One of us had shown 1 that the protoplasm is a colloidal fluid substance which reacts differently according to its immediate state of aggregation. The state of its aggregation is regulated by a substance or substances which is formed by the cells. This substance or substances has been called the archusia (S). In low concentrations (S1) the archusia has no effect. In medium concentration (S2) it causes the cells to migrate, to coagulate extracellular proteins, engorge themselves with proteins and fat particles, or to function. In high concentrations (S3) the cell digests these proteins and fats, absorbs water, grows and divides by mitoses. In all higher concentrations (S4) it causes the cells to disintegrate or suffer self-digestion. In the growth of the cell protein synthesis is not the only essential reaction, but the cell must also acquire or form a lipoid substance, the ergusia. This substance is essential for maintaining the structure of protoplasm. It is an active coagulant of protein. It is liberated by the cells in an (S2) concentration of the archusia. It is the active agent in the specific absorption of water and other substances necessary for growth, and the surface tension lowering substance necessary for the migration of the cells. The ergusia in excess in the tissue inhibits growth, as any substance, formed in any incomplete reaction, inhibits the reaction. It is also liberated by cells when they disintegrate as the result of a high concentration (S4) of the archusia. 2

Studies on Fatty Infiltration of the Liver Induced by Lipoid Solvents.

In a previous paper, Johnston and the author 1 reported that fatty infiltration of the liver occurs a certain period of time after the injection of a mixture of mineral oil and coal tar into the subcutaneous tissue of rats fed a diet rich in vitamin A. We thought at that time that this mixture of lipoid solvents alone produced the fatty infiltration in these animals. More recent studies have shown that this is not true. It was a time factor only which brought about the action of the mixture of mineral oil and coal tar. Later experiments have shown that other lipoid solvents will produce the same effect in the liver after a longer interval of time. A mixture of coal tar and paraffin produces the change 30 days after the injection, coal tar in 90 days, mazola oil in 60 to 90 days, mineral oil in 45 to 60 days, and a mixture of coal tar and mazola oil in 40 to 60 days. Thus, the time of occurrence of the fatty infiltration is governed by the particular kind of lipoid solvent used. At the times given above there is an extensive infiltration involving the entire parenchyma of the liver. Previous to this time in certain of the above series a few scattered areas of vacuolization were found in a few of the livers. The infiltration does not occur in the animals fed a ration deficient in vitamin A, and only to a slight degree in the animals fed a well balanced stock ration. It does not occur in rats fed a rich vitamin A dietary that are not injected with the substances listed above. These substances are lipoid solvents.

Relation of Dietary to Effects of Relatively Large Amounts of X-Rays on the Organism.

In a study of the effects of x-rays on animals fed normal dietaries, diets varying in the content of vitamins A and B and diets varying in relative amounts of the basic constituents, protein, fat and carbohydrates, certain findings have been obtained. As reported formerly, 1 10 MAM (13 “e” units) of x-rays given twice a week to a full grown or growing rat, prolongs and increases growth on a deficient vitamin B ration. 25 MAM (34 “e” units) increase growth and lengthen life on a ration deficient in either vitamin A or vitamin B. On 50 MAM (68 “e” units) the increase in normal growth and length of life is more marked in the series fed a dietary deficient in vitamin A than in one fed a dietary deficient in vitamin B. When larger doses than the above are given, such as 75 MAM (102 “e” units) or 100 MAM (136 “e” units) the life of the animal is shortened on either of these deficient rations. On a balanced laboratory ration life is shortened in each case, the degree of shortening being in direct ratio to the amount of x-rays given. On a stock ration consisting of dog biscuits, lettuce, carrots, meat and corn, the average length of life of a 90 gm. rat with the latter dosage is 90 to 120 days. As discussed in the communication cited above, these observations indicate that x-rays act to cause a protoplasmic breakdown within the cell. The apparent stimulation with the smaller dose is due to a predominance of the protoplasmic disintegration from which the energy of life is derived. When larger doses of x-rays are given, the greater splitting off occurs between the protoplasm and the ergusia, or vitamin A. With the smaller dose the splitting off occurs between the water soluble elements of the cell and the intercellular substances. In that a high vitamin A dietary does not wholly protect against these larger doses other structural elements of the cell must be destroyed also. This is illustrated by the observation that the usual balanced vitamin dietary protects for a shorter period of time than the well rounded stock ration. 2