E. L. Burns

Carcinoma-like proliferations in vagina cervix and uterus of mouse treated with estrogenic hormones.

We have referred 1 to the fact that in mice injected with preparations of estrogenic hormones over long periods of time abnormal proliferations of varying degrees of intensity may be induced not only in the mammary gland but also in certain parts of the vagina, cervix, and uterus. In a number of cases conditions were observed which in human beings would be considered precancerous lesions or as changes representing very early stages of cancer. In the monkey, Overholser and Allen 2 noted that in the cervix atypical epithelial proliferations were induced through administration of ovarian hormones. However, these investigators added traumatization of the tissue to the action of the hormones, while in our experiments the tissues were left intact. In two recent publications Lacassagne 3 described adenomatous proliferations of the uterine glands in the rabbit and in the mouse; in some cases the glands penetrated through the muscular layer. Quite recently we have autopsied a mouse in which proliferative changes had progressed further than in any of the others observed. This mouse, of the “Old Buffalo” strain in which spontaneous tumors are relatively rare, had been injected with estrogenic hormones for 24 months, 20 days, beginning at the age of 18 days. During the first 18 months this animal received 10 rat units of theelol in water daily; for the remaining 6 months, 20 days, daily injections of 30 rat units of theelin. At autopsy vagina, cervix, and uterus were very much enlarged. There were adhesions between the vagina and cervix and the surrounding pelvic tissues. Microscopic examination showed very extensive proliferation in the upper part of the vagina near the cervix, in various parts of the cervix, and in the uterus.

Incidence of Mammary Cancer and Nature of the Sexual Cycle in Various Strains of Mice.

Loeb and Genther 1 studied the characteristics of the sexual cycle in 2 different strains of mice, which were believed to differ in their incidence of mammary cancer. Subsequently it became doubtful to what degree the cancer incidence differed in these mice, and further-more a comparison of only 2 strains of mice did not seem sufficient. Soon after completion of this first series, we began therefore a new and more extensive series of experiments. In the meantime there appeared communications by Lacassagne 2 and by Harde, 3 which seemed to establish a connection between the differences in the intensity of follicular hormone action during the sexual cycle and the incidence of mammary cancer. Quite recently, however, Bonser 4 in comparing 2 strains of mice differing in the incidence of spontaneous tumors did not find any correspondence between these 2 conditions. Our own investigations are based on the study of 10 strains of mice markedly differing in their tumor incidence. We considered the following characteristics in the sexual cycle: (1) The duration of the sexual cycles and the number of cycles in individual mice, and the averages in the various strains. (2) The average duration of the periods of keratinization and the relation between the periods of oestrus and dioestrus in the various strains and in the individual mice composing them. (3) The degree of regularity of the oestrous cycles. We may summarize our results by stating that there was no parallelism noticeable between any of these factors and the incidence of mammary cancer either in the individual mice or in the whole strains. We studied the effect of 2 different diets on the characteristics of the sexual cycle. In a first period of 30 days, the mice were fed solely on a diet of Purina Chow; in a subsequent period of 28 days the diet consisted of a mixture of chow, cracked corn and oats.

Effect of Liver Extract on Thyroid Glands of Mice and Guinea Pigs

During experiments to test the effect of prolonged administration of liver extract on the blood-forming organs, attention was drawn to the thyroid gland by the hyperactivity and excitability of the animals so treated. The thyroid glands of 20 mice, injected daily with from 0.1 to 0.5 cc. of concentrated liver extract∗ for from 14 to 480 days, showed changes after 6 or 7 weeks of injection which progressed slowly but steadily as long as the injections were continued. These alterations consisted of; (1) Localized degeneration of several epithelial cells in some of the acini. (2) A general lowering of the height of the alveolar epithelium, associated with an increase in the amount of colloid contained in the acini. (3) Rupture of acini due either to pressure of an increased content of colloid inside the acinus or to isolated degeneration of the alveolar cells. (4) Accumulation of colloid material in the inter-acinar spaces, causing additional injury as well as compression, distortion, and separation of the acini. (5) A gradual increase in the amount of fibrous tissue in the stroma of the thyroid gland. No very definite changes have been noted in the thyroid glands of 6 guinea pigs injected daily for from 9 to 60 days, with from 0.5 to 1.0 cc. of concentrated liver extract. Whether injections for longer periods, or of larger doses, will produce alterations similar to those noted in mice is under investigation at present. While uninjected control mice showed none of the abnormalities noted in the experimental animals, it seemed possible that the thyroid changes produced by liver extract might be due to non-specific reactions which could also be elicited by extracts of other organs. Accordingly, a control extract was prepared from beef muscle, using the same method as that described for the preparation of liver extract. 1 To date, mice injected up to 90 days with this control extract have been studied.