Morphologic Studies on Adrenocortical, Tumors in Mice

Abstract

Virgin female mice of two strains; 67 of C₃H/He strain and 43 of ddY-F stain, were classified to the following four groups. ( 1 ) DMBA-injected; Both 20 C3H and 11 dd mice aged 6-7 weeks were injected into a caudal vein with a single dose,2.5 mg, of 7,12dimethylbenz (α) anthracene (DMBA). (2) Ovariectomized; Each 10 C3H and dd mice were ovariectomized at the age of 6-7 weeks. (3) Combination-treated; Both 24 C₃H and 13 dd mice were recieved with a bilateral ovariectomy at the age of 6-7 weeks and injected by 2.5 mg of DMBA 2 days later. (4) Control, untreated; Either 13 C3H or 9 dd mice were used. On these mice aged more than 30 weeks, several morphologic investigations were performed. The results are as follows.
I. Any adrenocortical tumors could not be found on the control, untreated mice aged even more than 72 weeks. But, so-called subcapsular cell reaction was detected already in almost all adrenal cortices over 30 weeks of age. The reaction was more in C₃H mice than in dd mice. The reaction, in general, was accerelated with aging and by the above mentioned treatments. It is supposed ultrastructurally that the proliferating subcapsular cells would be developed from the immature mesenchymal cells in this region.
II. Incidence of the adrenocortical tumor on the DMBA-injected group was 3/20 in C₃H mice and 1/11 in dd mice, respectively. All tumors were microscopically composed of Type A cell adenoma. The tumors looked to be adenomatous subcapsular cell reactions. Histological pattern of the target organs(uterus, vagina, kidney and submaxillary gland) of the mice bearing Type A cell adenoma could indicate that the tumor cells might not secret any hormones.
III. Ovariectomy at the age of 6-7 weeks induced a diffuse hyperplasia in the bilateral adrenal cortices. The hyperplasia was detected prominently on all C₃H mice aged over 25 weeke, but it showed less incidence and variable grade on the aged dd mice. Microscopically, the change developed from the inner zone of the adrenal cortex to the capsule, and it was mainly composed of large, round clear cell, Type B cell. Type b cell (immature Type B cell) could be identified ultrastructurally from Type B cell in the so-called Type B cell hyperplasia, and both hyperplastic cells were resemble to either the inner fasciculata or the reticularis cells. The histologic patterns of the target organs of the mice bearing so-called Type B cell hyperplasia were mainly male type, but those of few mice were female or intermediate type. Unilateral adrenocortical tumor was detected on the ovariectomized group (2/10 in C3H mice and 1/10dd mice), and all tumors had the similar appearance to cystic follicular type of the ovarian granulosa cell tumor. Prominent endometrial hyperplasia could be observed on the ovariectomized mice bearing such adrenocortical tumors.
IV. On the combination-treated group,5 adrenocortical tumors could be found only in C₃H mice. Administration of the carcinogen immediatedly after the gonadectomy could not potentiate the adrenocortilcal tumorigenesis in the female mice. Ultr astructural appearance of the induced tumor was Type A cell adenoma in 3 mice having no hyperhormonal findings, and mixed type adenoma in 2 mice, respectively. The latter was composed of adenomatous Type B cell proliferation and tubular arrangement of other cells (the author's Type a cell), and it might secret some sex hormones.
V. Brown degeneration was observed in almost all examined m ice aged more than 30weeks, and the change was more dominant in dd mice than in C₃H mice. The pigment granules, which were identified to lipofuscin histochemically, were accumulated mainly in the hypertrophic histiocytes and few in the degenerative reticularis cells. In conclusion, DMBA could not induce a neoplastic transformation in the mature, reactive adrenocortical cells,