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  • Polyamines and carcinogenesis
    Bachrach, Uriel

    Acta Facultatis Medicae Naissensis, 12/2012, Letnik: 29, Številka: 4
    Journal Article

    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. Poliamini, spermin, spermidin i diamin putrescin su jako rasprostranjeni u prirodnom obliku i uključeni su u procese rasta i diferencijacije. Da su ćelije kancera bogate poliaminima opisali smo 1967. godine. Ubrzo je prikazano da ćelije kancera ispuštaju poliamine i da se oni mogu detektovati u telesnim tečnostima poput urina, krvi i cerebrospinalne tečnosti. Takođe je prikazano da je porast ćelijskog nivoa poliamina rani i obavezni događaj u procesu maligne transformacije. Ovaj porast u ćelijskoj koncentraciji poliamina dešava se zbog aktivacije ornitin dekarboksilaze (ODC), koja katališe nivo limitirajuće stope u sintezi poliamina konvertovanjem ornitina u putrescin. Testiranje poliamina iz urina i krvi je rađeno u cilju otkrivanja kancera i određivanja uspešnosti terapije. Razvijena je senzitivna i brza metoda hemiluminiscencije za određivanje diamina i poliamina i testirano je 2000 uzoraka urina. Interesantan sistem ‘’genetske terapije’’ za ubacivanje amin oksidaze u normalne i transformisane ćelije razvijen je na sledeći način: serum amin oksidaze i diamin oksidaza dobijena iz svinjskog bubrega su zadržani u rekonstituisanim omotačima Sendai virusa. Fibroblasti embriona pileta ili pacova, izmenjeni virusom Rausovog sarcoma, bili su mnogo podložniji na ubačene enzime u poređenju sa normalnom podlogom, kada je testirana makromolekularna sinteza. Takođe je razvijen i in vitro test hemosenzitivnosti (‘’prilagođeni tretman’’) ćelija kancera kod različitih bolesnika. Sve ove studije naglašavaju značaj poliamina u karcinogenezi.