Arthur Kirschbaum

Endocrine Interrelationnship and Spontaneous Tumors of the Adrenal Cortex in NH Mice

Summary The occurrence of spontaneous estrogen-secreting tumors of the adrenal cortex can be correlated with early cessation of ovarian activity in the NH stock. Estrogen is probably secreted by the adrenal cortex even preceding adenoma formation. Gonadotrophic hormone enhanced estrogenic secretory activity of cortical adenomas.

Synergistic action of estrogenic hormone and X-rays in inducing thymic lymphosarcoma of mice.

Summary Synergistic lymphomogenic effects were obtained when estrogenic hormone and x-rays were administered simultaneously to mice of the Bagg albino and CBA stocks. Thymic lymphoid tissue appeared to be more sensitive than other lymphoid tissue. This was also true when x-rays and methylcholan-threne acted synergistically in the dba stock.

Effect of Urethane on Maturation of Leukocytes of Mouse Myelogenous Leukemia.

Summary The administration of a single anesthetic dose of urethane resulted within 24 hours in a drop in the white blood cell count and the appearance of many mature cells in the bone marrow of leukemic mice. Since the number of mitotic figures in marrow myeloid cells was decreased, maturation may have been secondary to inhibition of mitosis in blast cells. However, in the treated mice there were fewer marrow cells capable of undergoing division, which may account for the reduced number of mitoses. The release of an increased per cent of mature cells into the circulating blood may be a factor in depression of the white blood cell counts following the injection of urethane into mice with myeloid leukemia.

Relation of the Milk Influence to the Carcinogenic Induction of Mammary Cancer in Mice.

The administration of carcinogens to mice of inbred strains may result in the appearance of epitheliomas, sarcomas or other tumors to which the animals show no spontaneous susceptibility. In certain strains in which lung tumors, hepatomas, leukemia, or mammary cancer appear spontaneously carcinogens have accelerated their onset.1, 2, 3, 4

Androgenic secretion by tumors of the mouse adrenal cortex.

Summary A majority of gonadectomized male and female mice of the Bagg albino stock developed adrenal cortical tumors which secreted androgenic hormone. There is evidence that both androgenic and estrogenic hormone may be produced simultaneously by these tumors.

Genetic and Certain Non-genetic Factors with Reference to Leukemia in the F Strain of Mice.

MacDowell and Richter 1 found that the incidence of leukemia in hybrids could be roughly correlated with the total heredity from the high leukemia C58 strain when C58 mice were crossed with low leukemia StoLi animals. A “maternal influence” was suggested, for if the female parent was of the C58 strain the incidence of leukemia was greater than in the reciprocal cross. Cole and Furth, 2 working with the Ak and Rf stocks, concluded that susceptibility to leukemia is probably inherited as a multiple factor character, and is influenced by undetermined environmental factors. In various crosses the common logarithm of the percent leukemia was a simple function of the percent heredity from the high leukemia stock. Female mice had a higher incidence of leukemia than males. It was concluded that the genetic basis for spontaneous leukemia may vary for different stocks of mice, since Mercier 3 had observed that susceptibility to spontaneous lymphosarcoma was inherited as a simple Mendelian recessive character, and the results of MacDowell and Richter were somewhat at variance with those of Cole and Furth. In later experiments with the Ak stock Furth, Boon, and Kaliss 4 found that when animals of this stock were crossed with the C3H rather than the Rf stock the incidence of leukemia in F1 hybrids was higher, approximating that in the Ak stock, if the female parent was of the latter stock (50 as compared with 58%); the incidence of leukemia was 34% in F1 hybrids of the reciprocal cross. The present study was carried out using the F strain of mice as the high leukemia stock. 5 Of 325 control animals there were 173 cases of leukemia, or an incidence of 53%.

Influence of Breeding on Induction of Mammary Cancer with Methylcholanthrene in Strain Dba Female Mice.

Summary Mammary cancer appeared precociously in strain Dba female mice subjected to percutaneous applications of methylcholanthrene. The latent period was markedly shorter and the total incidence higher in breeding than in virgin animals.

Milk Influence and Leukemia in Mice.

Summary Preliminary, breeding experiments did not indicate that a specific “milkinfluence” (as for mammary cancer) is concerned in the development of leukemia in strain F mice. The incidence of leukemia in a group of 48 strain F mice fostered by low leukemia-strain mice was, however, somewhat lower than in unfostered controls of thesame strain.

Spontaneous Glomerulonephritis in Mice.

Although the clinical signs and symptoms, morphologic pathology, and the chemical alterations of the blood and body fluids are known in glomerulonephritis, investigations on etiology and pathogenesis have been retarded because experimental material has not been available. Spontaneous glomerulonephritis in animals has not been described; the disease has been induced in rats according to several investigators. 1 , 2 , 3 When mice of the Strong NH strain developed anasarca, ascites, and hydrothorax spontaneously, and became dysponeic, the condition was considered worthy of detailed study. Eight edematous animals of this strain were investigated from the morphologic standpoint. The kidneys were pale, but of approximately normal size and weight. On histologic section they revealed glomeruli with alterations strikingly similar to those seen in human chronic glomerulonephritis4-hyalinized glomeruli, and glomerular closure due to endothelial proliferation. These features were elucidated by staining with azo-carmine. In some cases not all the glomeruli were involved, whereas in others the process was general enough so that the term “diffuse glomerulonephritis” was applicable. Albuminuria was evidenced by casts in the tubules, but only a small degree of tubular degenerative change was present. Contracted kidneys have not been observed. Preliminary chemical study has confirmed the morphologic diagnosis. Albuminuria, decreased total plasma proteins (5.0 g as compared with a normal for the mouse of 6.2-6.5 g %), and hyperlipemia have been demonstrated for one typical case. The age of clinical appearance of the disease, when associated with edema, has ranged from 5 to 18 months; death ensued within 2 to 3 weeks in most cases after the development of massive edema. Glomerular pathology has been noted in animals which did not exhibit the nephrotic tendency. The incidence of the disease in untreated strain NH mice of the Minnesota stock has not been determined.† Further studies on the pathology of the disease in mice are being pursued; investigations on the genetic, chemical, bacteriologic, and nutritional aspects of the problem are being planned.

Assay of Methylcholanthrene-Induced Mammary Tumors of Mice for the Mammary Tumor Milk Agent.

Summary The mammary tumor milk agent was not demonstrable in the aqueous extracts of 4 mammary carcinomata induced by methylcholanthrene in female mice which were susceptible to the development of spontaneous mammary carcinoma but did not possess the milk agent before treatment because of foster-nursing. The action of the carcinogen was thus not dependent upon the presence of a milk agent.