ABSTRACT

The naturally occurring polyamines and the first and often rate-limiting enzyme regulating their synthesis, ornithine decarboxylase (ODC), are important for cell and tissue growth, particularly in small intestinal and colonic mucosa. Polyamine metabolism warrants further investigation as a biological tool to understanding the neoplastic process, and as a potential therapeutic target for colorectal malignancy. Ornithine is the precursor for the biosynthesis of the three naturally occurring polyamines, putrescine, spermidine, and spermine. It is decarboxylated by ODC to form putrescine, and this reaction appears to be the first and often rate-limiting step in polyamine biosynthesis. Increases in ODC activity and polyamine content in the intestinal mucosa are associated with cell growth and hyperplasia. Induction of ODC has been associated with carcinogenesis in animal models. The proliferation of human colonic carcinoma cells in culture, similar to other in vitro cell culture systems, is associated with increases in ODC activity and polyamine content.