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Consistent anorexia was first observed 33 days after inoculating Fischer 344 rats with methylcholanthrene-induced sarcoma. Daily treatment of a similar group of rats with the glutamine synthetase inhibitor, methionine sulfoximine, elicited significant reductions of feeding by day 29 at a dose that had no effect on nontumor-bearing rats. Blood concentrations of ammonia were elevated in both groups of tumor-bearing rats and brain ammonia level was increased in the methionine sulfoximine-treated tumor-bearing rats. Forebrain concentrations of tyrosine, tryptophan, DOPAC and 5-HIAA were elevated in both groups of tumor-bearing rats. Since ammonia is detoxified through the glutamine synthetase reaction, these results suggest that blood and brain ammonia concentrations are more important than the neurochemical consequences of ammonia detoxification for the etiology of cancer anorexia.

The enzyme activities of endogenous xanthine dehydrogenase (XDH) and xanthine oxidase (XO) have been measured in 10 different types of mouse tumour and seven normal tissues. The conversion of XDH to XO has been observed in two tumour types upon the prolonged clamping off of the blood supply to the tumours. It is proposed that a similar conversion might also occur naturally in chronically hypoxic cells and that the ratio of the XO activity to the combined XO + XDH activities (%XO activity) could well serve as a marker for tissue hypoxia. A qualitative relationship exists between the %XO activity and literature values of the hypoxic fraction for some tumours measured by radiobiological assays. The influence of tumour size (about 0.2-1.8 g) on %XO activity is presented for all 10 tumours as well as %XO activity determinations for four of the normal tissues.

In the cells of RS-1 carcinoma and those of Iensen's sarcoma it has been stated that acceleration and inhibition of tumor growth induced by nonspecific influence (vitamin A, hydrocortisone, proserin) are accompanied by uniform morphological changes of intracellular structures. Therefore, it is possible to suggest that the changes observed reflect a certain cell adaptation to the altering environmental conditions (cell stress-reaction). The cell stress-reaction is presented morphologically and hence, can by systematized. An attempt of such systematization is suggested.

Plasma concentrations of ammonia were elevated significantly in tumor-bearing rats prior to the onset of anorexia and continued to increase as the tumor grew and anorexia developed. Associated with this hyperammonemia were elevated levels of brain glutamine and large neutral amino acids (phenylalanine, tyrosine, tryptophan, methionine, histidine). Concentrations of the dopamine metabolites, DOPAC or HVA were elevated in the corpus striatum, nucleus accumbens, hypothalamus and amygdala of anorectic tumor-bearing rats only, while levels of the serotonin metabolite, 5-HIAA, were increased in these brain regions in both anorectic and non-anorectic tumor-bearing rats. Infusing ammonium salts into non-tumor-bearing rats elicited anorexia and alterations in brain amino acid profile and neurotransmitter metabolism that were similar to those observed in anorectic tumor-bearing rats. Therefore, we conclude that ammonia released by tumor tissue may have a direct role in the etiology of experimental cancer anorexia.

This report summarizes the data from two animal and cell culture systems that serve as models that show how certain malignant tumors produce hypercalcemia by means of a humoral mechanism. Studies with the HSDM1 murine fibrosarcoma and the VX2 carcinoma in the rabbit have led to the conclusion that these two tumors produce hypercalcemia in the host by means of a mechanism that utilizes prostaglandin E2 as the mediator between the neoplasm and bone. Analogous or identical mechanisms may operate in a small number of human tumors.