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

J Surg Res. 1999 Feb;81(2):181-8. doi: 10.1006/jsre.1998.5512.


Background: Colonic crypt cell hyperproliferation characterizes malignant and premalignant conditions of the colon and may be modified by dietary manipulation. This study compared the effect of dietary arginine supplementation on colonic crypt cell proliferation during the initiation and promotion stages 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 subcutaneous injections of 1, 2-dimethylhydrazine for 20 weeks. Group D received no arginine supplement. l-arginine was given as a 1% solution instead of drinking water to Group DA for 22 weeks, to Group FA for the first 10 weeks, and to Group LA for the last 12 weeks. EDTA animals were given subcutaneous injections of EDTA for 20 weeks. Colonic crypt cell proliferation was assessed in 6 animals from each of the five groups and in 6 normal rats not given DMH or EDTA.

Results: The BrdUrd-labeling index and proliferative zone were significantly 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 significantly lowered.

Conclusions: When given during the initiation phase of carcinogenesis l-arginine significantly reduced colorectal tumor production and crypt cell hyperproliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1,2-Dimethylhydrazine
  • Adenocarcinoma / chemically induced
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / prevention & control
  • Adenoma / chemically induced
  • Adenoma / pathology*
  • Adenoma / prevention & control
  • Animals
  • Arginine / pharmacology*
  • Carcinogens
  • Cell Division / drug effects
  • Colon / drug effects
  • Colon / pathology*
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / pathology*
  • Colonic Neoplasms / prevention & control
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / prevention & control
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology*
  • Male
  • Mitotic Index
  • Rats
  • Rats, Wistar


  • Carcinogens
  • Arginine
  • 1,2-Dimethylhydrazine