The production of polyamines has been shown to be an effective target for a drug against the West African form of sleeping sickness caused by Trypanosoma brucei gambiense. T. brucei belongs to the group of protozoan parasites classed as trypanosomatids. Parasitic species of this group are the causative agents of various tropical diseases besides African sleeping sickness, e.g. Chagas' disease (...

The mechanism of inactivation of rodent ornithine decarboxylase by a-difluoromethylornithine (DFMO) was studied using the inhibitor labelled with 14C in both the 1 and the 5 positions. [1-14C]DFMO was a substrate and was decarboxylated by the enzyme yielding '4CO2. A radioactive metabolite derived from [5-'4C]DFMO was bound to the enzyme, and the extent of binding paralleled the irreversible in...

Elevated polyamine levels are characteristic of many types of neoplastic cells and tissues. We demonstrate that in transgenic mice overexpressing ornithine decarboxylase in skin, changes in tissue polyamine levels, particularly putrescine, control the development and maintenance of the neoplastic phenotype. A specific inhibitor of the transgene, alpha-difluoromethylornithine (DFMO), reversibly ...

A gas-liquid chromatography (GLC) procedure for the detection of L-ornithine and L-lysine decarboxylase (EC 4.1.1.17 and EC 4.1.1.18, respectively) activities of bacteria was developed and evaluated against Møller's method, a conventional biochemical test. Cultures were incubated for 2 to 4 h in a simple growth medium and tested by GLC for putrescine and cadaverine, the direct decarboxylation p...

Trypanosoma brucei, the parasite that causes human African trypanosomiasis, is auxotrophic for purines and has specialist nucleoside transporters to import these metabolites. In particular, the P2 aminopurine transporter can also selectively accumulate melamine derivatives. In this Letter, we report the coupling of the melamine moiety to 2-hydroxy APA, a potent ornithine decarboxylase inhibitor...

Transgenic plants of Nicotiana tabacum L. homozygous for an RNAi construct designed to silence ornithine decarboxylase (ODC) had significantly lower concentrations of nicotine and nornicotine, but significantly higher concentrations of anatabine, compared with vector-only controls. Silencing of ODC also led to significantly reduced concentrations of polyamines (putrescine, spermidine and spermi...

The gene ODC1, which codes for the ornithine decarboxylase enzyme, was isolated from the entomopathogenic fungus, Metarhizium anisopliae. The deduced amino acid sequence predicted a protein of 447 amino acids with a molecular weight of 49.3 kDa that contained the canonical motifs of ornithine decarboxylases. The ODC1 cDNA sequence was expressed in Escherichia coli cells; radiometric enzyme assa...

The methylation state of CCGG sites in and around the human ornithine decarboxylase gene, oncogenes c-myc and erb-A1, and actin genes were determined in human malignant leucocytes from patients with acute and chronic myeloid leukemia, chronic lymphatic leukemia, polycythemia vera, and multiple myeloma by means of isoschizomeric restriction endonuclease analysis. When compared with DNA from leuc...

A rapid medium for the detection of lysine and ornithine decarboxylase and arginine dihydrolase activity of 439 strains of gram-negative, nonfermenting bacteria was evaluated and compared with Moeller decarboxylase medium. Results were obtained in 4 to 24 h using the rapid medium, whereas Moeller medium often required extended (3 to 7 days) incubation. There was 100% agreement in the lysine tes...

Cervical cancer remains a significant health problem. New strategies based on the molecular aspects of cervical carcinogenesis are needed. Chemoprevention represents a novel strategy for cervical cancer prevention. Our group plans phase I and II trials using alpha-difluoromethylornithine, a suicide inhibitor of ornithine decarboxylase and potent antiproliferative chemopreventive agent. We condu...