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

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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, stereologic 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 (> 5μ) 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 after initial detection. The adrenals of the tumor-bearing host exhibited marked involution, the extent of which was directly related to tumor size.