The effects of L-arginine on crypt cell hyperproliferation in colorectal cancer

Background. Colonic crypt cell hyperproliferation characterizes malignant a nd premalignant conditions of the colon and may be modified by dietary mani pulation. This study compared the effect of dietary arginine supplementatio n on colonic crypt cell proliferation during the initiation and promotion s tages of colorectal carcinogenesis. Materials and Methods. One hundred and twenty male Wistar rats were divided into 5 groups of 24 animals each. Groups D, DA, FA, and LA received subcut aneous injections of 1,2-dimethylhydrazine for 20 weeks. Group D received n o arginine supplement. L-arginine was given as a 1% solution instead of dri nking water to Group DA for 22 weeks, to Group FA for the first 10 weeks, a nd to Group LA for the last 12 weeks. EDTA animals were given subcutaneous injections of EDTA for 20 weeks. Colonic crypt cell proliferation was asses sed in 6 animals from each of the five groups and in 6 normal rats not give n DMH or EDTA. Results. The BrdUrd-labeling index and proliferative zone were significantl y decreased in all arginine groups (DA, FA, LA). The greatest reduction was evident in Group FA in which tumor incidence and tumor size were also sign ificantly lowered. Conclusions. When given during the initiation phase of carcinogenesis L-arg inine significantly reduced colorectal tumor production and crypt cell hype rproliferation. (C) 1999 Academic Press.