Presence of tumour inhibits the normal post-operative response in arginine and NO production in non-cachectic mice

We have described recently that cancer patients have low plasma arginine concentrations, even without weight loss being present, suggesting that decreased arginine availability may be a specific feature of the presence of tumour. As arginine is important in post-operative repair, we hypothesized that abnormalities in arginine metabolism in cancer lead to an aberrant post-operative response in arginine and NO metabolism. To investigate this, we studied post-operative alterations in arginine and NO production and the acute-phase response in MCA (methylcholanthrene) sarcoma-bearing mice. Controls, mice with small MCA tumours (<15% of carcass weight) and large MCA tumours (>15% of carcass weight) were studied, either with or without undergoing laparotomy. The stable isotopes L-[guanidino-(15)N(2)-(2)H(2)]arginine and L-[ureido-(15)N]citrulline were used to study whole-body arginine and NO production rates. SAP (serum amyloid P component) concentrations were measured to assess the acute-phase response. Significance was tested using Mann-Whitney U test. In healthy FVB mice, laparotomy significantly increased whole-body arginine production (from 42+/-3 to 54+/-3 nmol x 10 g(-1) of carcass weight x min(-1)), NO production (from 1.1+/-0.1 to 1.4+/-0.2 nmol x 10 g(-1) of carcass weight x min(-1)) and levels of SAP (from 4+/-1 to 115+/-23 ng/ml), whereas in all MCA tumour-bearing mice baseline values of arginine metabolism and SAP concentration were already elevated and the response to laparotomy was absent. In conclusion, MCA tumour-bearing mice had a disturbed post-operative metabolic response, as evidenced by attenuated post-operative arginine and NO production, concomitant with an attenuated acute-phase response. This indicates that altered arginine metabolism may be an important characteristic of the metabolic changes in cancer.