Polyamines and carcinogenesis

Abstract

The naturally occurring polyamines, spermine, spermidine and the diamine putrescine are widespread in nature. They have been implicated in growth and differentiation processes. In 1967, we reported that cancer cells are rich in polyamines. Subsequently, it has been shown that polyamines are released from cancer cells and may be detected in body fluids such as urine, blood and cerebrospinal fluids. It has also been demonstrated that the increase in cellular polyamine levels is an early and an obligatory event in the process of malignant transformation. This increase in cellular polyamine concentration is due to the activation of ornithine decarboxylase (ODC), which catalyses the rate limiting step in polyamine synthesis by converting ornithine to putrescine. Assays of urinary and blood polyamines have been used to detect cancer and to determine the success of therapy. A sensitive, rapid, chemiluminescence-based method for the determination of diamines and polyamines was developed and 2.000 urine samples were tested. An interesting "gene therapy" system for injecting amine oxidases into normal and transformed cells was developed as follows: serum amine oxidase and porcine kidney damine oxidase were trapped within reconstituted Sendai virus envelopes. Chick or rat fibroblasts, transformed by Rous sarcoma virus, were more susceptible to the injected enzymes, compared to the normal culture, when macromolecular synthesis was tested. An in vitro chemosensitivity assay for the testing of the sensitivity of cancer cells from individual patients ("tailored treatment") was also developed. All these studies stress the importance of polyamines in carcinogenesis.

The critical role of the aldehyde dehydrogenase PauC in spermine, spermidine, and diaminopropane toxicity in Pseudomonas aeruginosa: Its possible use as a drug target

“…The polyamines putrescine (Put), cadaverine (Cad), spermine (Spm), spermidine (Spd), and diaminopropane (Dap) are among the great variety of compounds in which P. aeruginosa can grow as its only carbon and nitrogen sources [5][6][7]. These polyamines are present in tissues infected by P. aeruginosa [8][9][10] and have been found in increased levels in physiologic fluids such as blood and urine in patients with cystic fibrosis [11][12][13] or cancer [14,15], the latter known to be highly susceptible to P. aeruginosa infections when under chemotherapy [1,16]. Moreover, increased Spm concentrations in the sputum of cystic fibrosis patients were reported [17].…”