Inappropriate secretion of antidiuretic hormone in nude mice bearing a human bronchogenic oat cell carcinoma.
A 58-year-old man with bronchogenic oat cell carcinoma developed a typical syndrome of inappropriate secretion of antidiuretic hormone. The tumor tissue obtained at autopsy had been serially transplanted in nude mice for more than four years with 20 passages. The levels of vasopressin were remarkably increased in the plasma of nude mice bearing this tumor [24.4 +/- 18.3 (S.D.) pg/ml, n = 3] as well as in the tumor tissues ]134.3 +/- 72.2 ng/g, n = 3]. Furthermore, human nicotine-stimulated neurophysin was detected in both plasma and tumor tissues (7.4 +/- 3.7 ng/ml, n = 3, and 2.28 +/- 0.90 micrograms/g, n = 3, respectively). On ad libitum intake of water, nude mice bearing this tumor excreted significantly less urine with higher sodium concentration than did controls, but serum sodium concentrations did not differ from those of controls. When tumor-bearing mice were hydrated with 2 ml of water twice a day i.p., their diuretic response was found to be suppressed in parallel with the tumor size. However, these mice did not become hyponatremic because they drank less water. When a larger amount of water was loaded which could not be compensated by restriction of water drinking, serum sodium concentrations were markedly decreased. On the basis of these results, the lung cancer, when transplanted into nude mice, produced and secreted its own antidiuretic hormone, which induced inappropriate secretion of antidiuretic hormone in the mice. These mice may provide a useful experimental model for the study of excessive secretion of antidiuretic hormone and associated pathophysiological disorders.