Effect of Supplemental l‐Arginine in a Chemical‐Induced Model of Colorectal Cancer

Abstract

L-Arginine inhibits the development of spontaneous, transplantable solid tumors and chemically induced mammary tumors. The aim of the present study was to investigate the effect of l-arginine on chemically induced colorectal cancer in male Wistar rats. Colorectal cancer was induced in all animals by weekly subcutaneous injections of the colonic procarcinogen 1,2-dimethylhydrazine (DMH) at a dosage of 20 mg/kg body weight. Arginine was given in a 1% solution of drinking water. Group I was the DMH control; group II, arginine for 22 weeks; group III, arginine for the first 10 weeks only. Lymphocyte function was evaluated by measuring the thymic lymphocyte proliferative response to the T cell mitogen phytohemagglutinin. The results show that tumor incidence and tumor burden (tumors/rat and tumors/tumor-bearing rat) were significantly reduced in both groups of animals receiving arginine compared to DMH controls (p < 0.05). The tumor areas and volumes were also reduced in both arginine groups (p < 0.05). Thymic lymphocyte stimulation indices were significantly increased by arginine supplementation (p < 0.05). These results would be in keeping with the reduction in colorectal tumor production due to a "nonspecific" stimulation of the host immune system by L-arginine.

The Effects ofl-Arginine on Crypt Cell Hyperproliferation in Colorectal Cancer

“…The location, area (size), macroscopic type, tumor architecture, number of blood vessels, and inflammatory infiltrate of all tumors were described by a single pathologist (D.O'R.). The volume of tumors was calculated as described [31]. The area was calculated after the tumor was divided into two-one portion for cell proliferation studies and one portion for morphological assessment.…”

“…L-arginine, a semiessential amino acid, reduces tumor production in some tumor models including chemically induced and transplantable solid tumors [27][28][29][30][31]. Arginine's effect on host-tumor interaction, which has been correlated with immune enhancement, appears to be optimal at supplemental concentrations between 0.5 and 1% [30,32].…”

Differential Inhibitory Effects of the Polyphenol Ellagic Acid on Inflammatory Mediators NF‐κB, iNOS, COX‐2, TNF‐α, and IL‐6 in 1,2‐Dimethylhydrazine‐Induced Rat Colon Carcinogenesis

“…Besides a genetic pre-disposition, diet also determines the risk for colon cancer and predominantly diets rich in fruits and vegetables diminish the risk of the disease [3]. 1,2-Dimethylhydrazine-induced model is utilized frequently, as it is similar to histopathological and molecular characteristics of human colon cancer model [4]. 1,2-Dimethylhydrazine is metabolized in liver to form azoxymethane and methylazoxymethanol later on transported to colon via bile or blood to generate its ultimate carcinogenic metabolite, diazonium ion which elicits an oxidative stress by methylating biomolecules of colonic epithelial cells and leads to promutagenic events as a result of inflammation and tumours in colon [5].…”

A novel mouse model for colitis-associated colon carcinogenesis induced by 1,2-dimethylhydrazine and dextran sulfate sodium

“…Animal studies showed that experimental colonic tumors induced by DMH were of epithelial origin with a similar histology, morphology and anatomy to human colonic neoplasms [14] . This procarcinogen could thus provide an adequate model for studying colorectal cancer.…”