Effect and mechanism of L-arginine on experimental colorectal cancer

Objective: The effect of arginine on chemical-induced colorectal carcinogenesis was investigated in Wistar rats. Methods: Colorectal cancer was produced by weekly subcutaneous injections of carcinogen 1,2-dimethylhydrazine(DMH) for 20 weeks. Arginine was given in 1% solution either whole experimental period for 22 weeks or only during last 12 weeks. EDTA-treated animals were as controls. Tumor characteristics, peripheral lymphocyte responses to mitogen PHA, T-cell subsets(CD2, CD4, CD8)and plasma gastrin concentration were studied. Results: No EDTA animals developed tumors. Adenoma areas and volumes were not different among DMH-treated animals, but adenocarcinoma areas and volumes in both arginine-fed groups were significantly reduced compared with DMH controls (P < 0.02). Adenocarcinomas beyond submucosa were the lowest in the group fed arginine during whole experimental period (P < 0.05). Arginine given in both EDTA-treated animals and during whole experimental period of DMH-treated animals significantly stimulated lymphocyte mitogenesis and increased T-cell subset distribution while arginine given during last 12 weeks did not. The ratio of CD4/CD8 and plasma gastrin concentration were not changed by arginine supplementation. Conclusion: The reduced carcinogenesis by L-arginine might be related to its non-specific stimulation of host lymphocyte function and it is unlikely to be associated with gastrin secretion.