Rat adrenocortical carcinoma 494: An integrated structural, stereological, and biochemical analysis

Abstract

Snell adrenocortical tumor 494 was implanted into male Sprague-Dawley rats and recovered 7, 14, 21, 28 or 35 days following initial detection by palpation (7-10 days following transplantation). Electron microscopic, stereological and biochemical analyses of the tumor were compared to adrenals of normal animals to serve as a baseline for further studies of the effects of chemotherapeutic agents on tumor cells. Tumor cells possessed oval or elongated mitochondrial profiles with tubular cristae, one or two very large (greater than 5 micrometer) lipid droplets, abundant ribosomes and coated vesicles, and sparse rough and smooth endoplasmic reticulum. Stereologic evaluation revealed that tumor lipid volume was 41% and mitochondrial volume 29% that of the normal adrenal controls. Tumor nuclei were 2.5 times larger than adrenocortical nuclei while cellular volumes were similar. On a net weight basis, tumor cholesterol was 55%, cholesterol ester 2.2%, and lipid phosphate 25% of respective mean values for normal adrenal glands. The tumor cholesterol: cholesterol ester ratio progressively decreased with time but remained 18-fold greater than the normal adrenal. Plasma corticosterone levels in tumor-bearing rats were elevated 3-fold by 14 days and initial detection. The adrenals of the tumor-bearing host exhibited marked involution, the extent of which was directly related to tumor size.

Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

“…Nearly two-thirds of diagnosed patients are women. There are numerous reports in the literature describing animal models of adre-nal carcinoma (4)(5)(6)(7)(8)(9). Comparatively few biochemical studies, however, have been reported with primary human tumors (10)(11)(12)(13)(14), although a substantial literature now exists concerning the clinical presentation, diagnosis and treatment of this disorder (15)(16)(17)(18)(19).…”