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Chemical and Histochemical Study of the Effect of Transplanted Tumor upon Activity of Adrenal Nicotinamide Adenine Dinucleotide Phosphate Diaphorase in Rats¹

( Section of Experimental Pathology, Department of Pathology, The University of Texas, M. D. Anderson Hospital and Tumor Institute, Houston, Texas)

Chemical and histochemical studies were conducted to determine the effect of progressive tumor growth upon the activity of the diaphorase of reduced nicotinamide adenine dinucleotide phosphate (NADPH) in the adrenal glands of the host. Walker carcinosarcoma 256, Novikoff hepatoma, and a new hepatoma induced in our laboratory were transplanted into male Sprague-Dawley rats. As the tumors grew, the activity of the enzyme in the cortices became elevated in conjunction with adrenal hypertrophy and thymic involution. Similar results, other than in the zona glomerulosa, were obtained in studies of the adrenal glands of tumor-free rats receiving injections of adrenocorticotropic hormone (ACTH). Adrenal hypertrophy and thymic involution, as well as the high enzymatic activity in the inner cortical zones, caused by the tumor growth, were inhibited by hypophysectomy. Interestingly, the high activity of the enzyme in the glomerulosa was observed not only in tumor-bearing intact rats, but also in tumor-bearing hypophysectomized rats. In addition, this increased activity appeared in a much earlier stage of tumor growth than that observed in the inner cortices of tumor-bearing intact animals. The activity in the glomerulosa of tumor-free intact and of tumor-free hypophysectomized rats, however, was increased only slightly by injections of ACTH.

From these enzymatic patterns, it appears that tumor growth affects the activity of the NADPH diaphorase in the glomerulosa of the adrenal cortex by an unknown pathway; in the fascicular and reticular zones the effect appears to be mediated through the pituitary-adrenal axis.

¹ This research was supported by Public Health Service grant CA 05312 from the National Cancer Institute. Reported in part at the 55th Annual Meeting of the American Association for Cancer Research, Chicago, Ill., April 9–11, 1964.

² Present address: Hokkaido University, Sapporo, Japan.

Received 8/ 6/64. Revised 1/ 4/65.