Degradation of insulin and glucagon by a factor associated with Walker 256 carcinosarcoma cells.

Earlier studies from this laboratory reported that, in rats bearing the Walker 256 carcinosarcoma, circulating insulin levels were significantly reduced relative to non-tumor-bearing rats. The present study extends this observation to include a significantly (P less than 0.01) reduced plasma level of glucagon in rats bearing the tumor for both 7 and 10 days. In order to determine if the tumor itself somehow plays a role in the degradation of these protein hormones, either cultured Walker 256 tumor cells (in the case of the insulin studies) or cells from freshly excised tumor (for the glucagon studies) were incubated with 125I-labeled insulin or glucagon. Following the incubation period, the amount of TCA-precipitable radio-label remaining in the incubation medium was markedly reduced after exposure to cells. This suggests that the tumor cells have the capability of degrading both insulin and glucagon. In a separate series of experiments, it was found that medium, in which freshly excised tumor cells had been incubated previously and then discarded, retained a substance which degraded 125I-labeled glucagon and that this degradation of glucagon could be blocked by co-incubation with aprotinin, a protease inhibitor.

Hormones of the pituitary-adrenal axis in rats bearing the Walker 256 carcinoma.

Male Sprague-Dawley rats (125-150 g) were implanted intramuscularly with the Walker 256 carcinoma. After 3, 5 or 7 days, tumor-bearing rats, along with controls, were killed and plasma levels of adrenocorticotropic hormone (ACTH), beta-endorphin and corticosterone were assessed. Plasma levels of all 3 hormones declined with time following tumor implantation. Plasma levels of ACTH and corticosterone were statistically significantly less than plasma levels of these same hormones in control rats by 7 days post-implantation. Levels of these hormones were reduced by 42% and 33%, respectively, relative to control levels by 7 days. beta-Endorphin levels declined much more rapidly following tumor implantation than did either of the other 2 hormones. beta-Endorphin was significantly decreased by 3 days post-implantation and by 7 days the plasma levels of this factor were 83% lower than in control rats.

Insulin-stimulated glucose utilization in adipose tissue from rats bearing Walker 256 carcinoma.

Male Sprague-Dawley rats (125--150 g) were implanted intramuscularly with Walker 256 carcinoma. After 10--14 days, tumor-bearing rats, alone with controls, were killed and the ability of insulin to promote the in vitro utilization of glucose by epididymal adipose tissue was assessed. The sensitivity of free adipocytes and minced adipose tissue from tumor-bearing rats to insulin, as assessed by measurement of the incorporation of glucose into total lipids as well as into the triglyceride fraction of neutral lipids, was significantly less (P less than 0.01) as compared to control animals. Similarly, insulin was considerably less effective at enhancing glycogenesis in vitro in adipose tissue from animals bearing the tumor for 10 days compared to adipose tissue from controls. Adipose tissue from tumor-bearing animals tended to convert less glucose to CO2 in the presence of insulin than did adipose tissue from controls. That this decreased in vitro sensitivity to insulin of adipose tissue from tumor-bearing animals could be the result of simple down-regulation by high levels of circulating insulin can be ruled out by the fact that the presence of the tumor resulted in lower circulating insulin than that in control animals. Serum glucose levels were also lower in tumor-bearing rats than in corresponding control animals.

Neoplasms in rats and mice fed butylurea and sodium nitrite separately and in combination.

In projected 485-day studies, Fischer 344 rats and C57BL/6 mice were fed 0.58% butylurea and 0.50% sodium nitrite mixed in the diet separately or in combination. The number and type of neoplasms were not significantly increased in either species receiving butylurea or sodium nitrite only. Feeding the two chemicals simultaneously induced neoplasms of the lung, Zymbal's gland, forestomach, intestine and hemopoietic tissues in rats, and malignant lymphomas in mice. The increased incidence of neoplasms in rats and mice fed butylurea and sodium nitrite in combination may result from in vivo formation of the carcinogen, N-butyl-N-nitrosourea.