Leopold R. Cerecedo

Essential Fatty Acid Deficiency in the Mouse

Summary Albino mice kept on a diet devoid of fat developed the Burr and Burr syndrome. The deficiency could be cured or prevented by the administration of lard.

Chemical Changes in Tumor-Bearing Mice.∗

Summary 1. The nucleic acids, purines, pyrimidines, and methionine, arginine, histidine, threonine, glycine, and cystine have been determined in various tissues of mice of the Swiss strain bearing transplanted sarcoma 180 (Crocker). 2. The changes in the nucleic acid content of the tissues are paralleled by the values for the individual purines and pyrimidines. In the liver and lung of mice bearing sarcoma, there is an increase in both RNA and DNA, and this increase is further confirmed by the corresponding increases in uracil and thymine. The fact that only the DNA content of the kidney increases is further supported by an increase in the thymine values alone, while the uracil content of this organ remains unchanged. 3. The values for thymine when expressed as per cent of DNA, suggest that the composition of DNA in the liver, lung, and kidney is the same. 4. The study of the amino acids present in a sarcoma and in the tissues of normal and sarcoma-bearing mice reveals that there are significant changes in the amino acids of the tissues of tumor bearing animals. In the sarcoma, there is a significant increase in arginine and glycine, the values for the second and third week being higher than those for the first week. In the livers of these animals, there is a significant increase in arginine, histidine, threonine, glycine, and cystine over the normal controls. In the lung, the increase is noted in arginine, threonine, and cystine, while there is a drop in the histidine content, as the tumor progresses. Arginine alone shows a significant increase in the kidney, while in the spleen none of the amino acids studied shows any change over the normal control values.

Nucleic Acid Changes in Tumor-bearing Mice.

Summary 1. The nucleic acid content of various tissues has been determined in mice of the Swiss and dba strains bearing transplanted sarcoma 180 (Crocker), in dba mice bearing malignant melanoma S-91, and in Swiss mice bearing spontaneous mammary tumors. 2. In the mice with transplanted tumors, an increase in the pentose nucleic acid (RNA) and desoxypentose nucleic acid (DNA) content of the liver and lung was observed, whereas the kidneys showed a similar rise in the DNA. In the mice with mammary tumors, the most marked increase was found in the lung nucleic acids. 3. The changes of the nucleic acids in the dba mice could be related to the size and the rate of growth of the tumor. 4. The ratio RNA/ DNA in the tumor usually dropped with the growth of the tumor. This drop is attributed to a decreased concentration of RNA in both the necrotic and non-necrotic portions of the tumor, whereas the DNA content dropped only in the necrotic portion. 5. The nucleic acids, purines, and pyrimidines in malignant melanoma S-91 have been determined at various stages of its development. The lower values for uracil and thymine found in the necrotic portion of the tumor as compared with those found in the non-necrotic portion point also to a drop of both RNA and DNA in the necrotic portion.

The nutritive value of Fusaria.

It has been shown that Fusarium lini B. grown on an artificial stock culture medium when supplemented with thiamin provides adequate amounts of the B-complex vitamins for normal growth, reproduction and lactation in mice, and that it compares very favorably with brewers yeast in its food value.

Nucleic acids and their components in tumor-bearing mice during growth and regression of tumors.

Summary 1. The concentration of ribose nucleic acid (RNA), desoxyribose nucleic acid (DNA), adenine, and guanine of liver, lung, kidney, and spleen of normal C3H mice and those bearing a transplantable mouse lymphosarcoma at different stages of tumor development has been determined. The mice bearing the tumor were divided into 2 groups; one group received desoxypyridoxine on a vit. B6 deficient diet, while the other received desoxypyridoxine on a diet rich in vit. B6 to counteract the effect of the anti-vitamin. In addition to DNA, RNA, adenine, and guanine, the pyrimidines (uracil, cytosine, and thymine) were also determined in the spleen. 2. The data presented indicate that there is an increase in the nucleic acids and their purine constituents in the liver, kidney, and lung during the growth of the tumor. 3. The nucleic acids reached a higher level in mice receiving desoxypyridoxine on a vit. B6 sufficient diet than in mice receiving desoxypyridoxine on a vit. B6 deficient diet. 4. Mice receiving desoxypyridoxine on a diet high in vit. B6 show a maximum value in DNA (which is close to normal) in the spleen on the 17th day of tumor growth which then drops to approximately 20% below normal at 19 days. In mice receiving desoxypyridoxine on a diet deficient in vit. B6, DNA in the spleen drops quite sharply. At 19 days, this drop is over 70% below normal and this is followed by a similar drop in thymine, cytosine, guanine, and adenine. RNA does not vary to a significant extent in the spleen, and this is also true of uracil. 5. The changes in nucleic acids are followed generally by similar changes in adenine and guanine.

Tumor-host relations during development and after regression of the tumor.

Abstract Chemical and physiological changes occurring during development and after regression of the Murphy-Sturm lymphosarcoma, and the Jensen sarcoma, in the rat, and of a myeloid leukemia in the mouse, have been studied. Growth of the Murphy-Sturm lymphosarcoma is accompanied by an increase in the deoxyribonucleic acid (DNA) content of liver, lung, and spleen, and a decrease of DNA in the bone marrow. Of the tissues mentioned, spleen alone shows a change in the concentration of ribonucleic acid (RNA), namely, an increase. The potassium concentration of liver also rises. During the development of the Jensen sarcoma, there is a rise in the concentration of DNA in the lung, while RNA remains unchanged. Hemoglobin, specific gravity, and total solids of the blood are markedly depressed and attain minimum levels when tumor size has reached 20% of the body weight. Myeloid leukemia has no effect on the DNA of liver or kidney in the mouse, but induces a rise in lung DNA and a decrease in DNA of the spleen. The RNA does not show a change in any of these tissues. When the three afore-mentioned tumors undergo regression, each of the above changes is reversed and normal patterns are re-established.

Metabolism of thiamine-S35 in the rabbit.

Summary The fate of thiamine, labeled with sulfur-35 in the thiazole moiety, has been studied in rabbits after oral and parenteral administration of doses in the physiological range. Analyses of the urinary and fecal sulfur fractions for 4 to six 24-hour periods following administration of radiovitamin, gave average total recovery of radiosulfur of 77% after administration by stomach tube, 86% after intramuscular injection, and 54% after intravenous injection. When oral dose of radiovitamin was followed 6 hours later by intramuscular injection of a 20-fold larger dose of non-radioactive thiamine, an additional 17% of radiosulfur was recovered in urine. In all cases, the neutral sulfur fraction of urine contained more than 50% of the recovered radiosulfur, and the greater portion of this was excreted in the first 24-hour period following administration of radiovitamin. Isolation of main metabolites following oral administration indicates that unchanged thiamine-S35 and thiazole S35 moiety together account for approximately 95% of radiosulfur of the neutral sulfur fraction in the first 24-hour period, and are excreted in a ratio of 2 : 1, respectively.

Effects of Desoxy- and Methoxypyridoxine in the Mouse.∗

Summary (1) Desoxypyridoxine has been shown to exert a powerful antipyridoxine effect in the mouse. With the aid of this substance, typical symptoms of vitamin B6 deficiency (acrodynia) have been produced in this species. (2) A high casein level in the diet was found to have a detrimental effect on the acrodynia thus produced, but not to the same extent as that observed in the case of the acrodynia of vit. B6 deficient rats, not receiving desoxypyridoxine. Methionine, in amounts equivalent to those present in the casein, had a corresponding detrimental effect. (3) The pyridoxine requirement of the mouse was found to be, under the conditions of our experiments, between 1 and 2 γ per day. (4) For mice receiving 2 γ pyridoxine per day, the inhibition index of desoxypyridoxine was found to be 10. (5) Methoxypyridoxine acts as a pyridoxine precursor in the mouse.

Chemical changes in the lungs of tumor-bearing rats☆

Abstract The nucleic acids were determined in the lungs of rats bearing the Walker 256 tumor, and or rats bearing the Murphy-Sturm lymphosarcoma. Significant increases in the desoxyribonucleic acid (DNA) concentration during the growth of the tumors were observed. In contrast, the ribonucleic acid, protein nitrogen, potassium, and cholesterol did not show any change.

Effects of certain thiamine analogs on the enzymatic decarboxylation of α-ketobutyric acid☆

Abstract The effects of neopyrithiamine, oxythiamine, and oxythiamine diphosphate on the decarboxylation of α-ketobutyrate by α-carboxylase have been studied. Oxythiamine diphosphate, but not oxythiamine or neopyrithiamine, inhibited the decarboxylation. The inhibition was dependent upon the order of addition of cocarboxylase and analog to the reaction mixture.