Cloning of genes related to polyamine metabolism has enabled the generation of genetically modified mice and rats overproducing or devoid of proteins encoded by these genes. Our first transgenic mice overexpressing ODC (ornithine decarboxylase) were generated in 1991 and, thereafter, most genes involved in polyamine metabolism have been used for overproduction of the respective proteins, either...

Chemoprevention is the long-term use of different chemical agents, both synthetic and natural, to prevent or delay the onset of disease. Since colorectal cancer has a significant environmental component, it is an ideal disease in which to evaluate the potential benefits of chemopreventive agents. The polyamines, spermine, spermidine and putrescine have been involved in almost all the steps of c...

The role of ornithine decarboxylase (ODC) in polyamine metabolism has long been established, but the exact source of ornithine has always been unclear. The arginase enzymes are capable of producing ornithine for the production of polyamines and may hold important regulatory functions in the maintenance of this pathway. Utilizing our unique set of arginase single and double knockout mice, we ana...

One strategy for inhibiting tumour cell growth is the use of polyamine mimetics to depress endogenous polyamine levels and, ideally, obstruct critical polyamine-requiring reactions. Such polyamine analogues make very unusual drugs, in that extremely high intracellular concentrations are required for growth inhibition or cytotoxicity. Cells exposed to even sub-micromolar concentrations of such a...

Although the intracellular de novo synthesis of the polyamines decreases with age, there is no similar trend in blood polyamine levels, but rather there is wide individual variability. We hypothesized that dietary polyamines attenuate a decrease in blood polyamine levels with age and augment the previously observed individual variability. The effect of a polyamine rich diet, in both mice and hu...

We recently identified a gene (TPO1, YLL028w) that encodes a polyamine transport protein on the vacuolar membrane in yeast [Tomitori, Kashiwagi, Sakata, Kakinuma and Igarashi (1999) J. Biol. Chem. 274, 3265-3267]. Because the existence of one or more other genes for a polyamine transport protein on the vacuolar membrane was expected, we searched sequence databases for homologues of the protein ...

OBJECTIVE Activation of polyamine metabolism is closely associated with cellular proliferation. The purpose was to investigate whether the content of the polyamines putrescine, spermidine, and spermine, and the activity of the first metabolic key enzyme of polyamine metabolism, ornithine decarboxylase (ODC), represent biochemical markers of malignancy in brain tumours. METHODS The concentrati...

Colorectal cancer is one of the most common cancers in the world. It is well known that the chronic inflammation can promote the progression of colorectal cancer (CRC). Recently, a number of studies revealed a potential association between colorectal inflammation, cancer progression, and infection caused by enterotoxigenic Bacteroides fragilis (ETBF). Bacterial enterotoxin activates spermine ox...

W. E. Hull, M. Wolf, S. Heiland, U. Bauder-Wuest, M. Eisenhut Central Spectroscopy, German Cancer Research Center (DKFZ), Heidelberg, Germany, Radiopharmaceutical Chemistry, German Cancer Research Center (DKFZ), Heidelberg, Germany, Experimental Neuroradiology, University of Heidelberg, Heidelberg, Germany Introduction Conventional paramagnetic MRI contrast agents such as [Gd(DTPA)(H2O)] 2– (Ma...

Increased polyamine biosynthesis activity and an active polyamine transport system are characteristics of many cancer cell lines and polyamine depletion has been shown to be a viable anticancer strategy. Polyamine levels can be depleted by difluoromethylornithine (DFMO), an inhibitor of the key polyamine biosynthesis enzyme ornithine decarboxylase (ODC). However, malignant cells frequently circ...