Variability of polyamine metabolic balance during experimental and human tumor development
Summary. Introduction. Inhibitors of the enzymes of the polyamine (PA) biosynthesis and back-conversion are known as a kind of the effective anticancer remedies. But real conditions of the enzymatic reaction balance variability in the PA metabolic system during the tumor development are still studied insufficiently. The end expression of this enzymatic balance is a pattern of the PA spectrum in the tumor tissue and in the biological fluids of the tumor-bearing organism. Aim of research. Тo compare the PA spectrum patterns variability during experimental and clinical tumor development of different aetiology and location. Methods of research. PA spectrum patterns were studied during three kinds of experimental chemical carcinogenesis (N-nitrosodiethylamine liver carcinogenesis; 1,2-dimethyl hydrazine large and small intestine carcinogenesis) in rats as well as in the operational materials and urine of the patients with mammary, lung and rectal cancer. PA content in the biological materials was measured by the methods of thin-layer chromatography and high performance liquid chromatography, ornithine decarboxylase (the key enzyme of the PA biosynthesis) activity — by radiometric determination of CO2 production and/or chromatographic determination of putrescine production. Student’s t-criterion and, in need, Fisher’s exact method were used for statistical data treatment. Results and Discussion. Statistically significant modulations of PA spectrum were discovered during all kinds of tumor development have been studied. The modulation patterns were found to be significantly different dependently on the kind of tumor. Because of ambiguity of the PA spectrum mapping into the set of the enzymic balance stages (each pattern of PA spectrum may be obtained in two or more combinations of the enzyme activities), real optimization of the «antipolyamine» therapy require detailed enzymological investigations. Conclusion. Our resuts demonstrate significant and tumor-kind-dependent modulations of the PA balance during tumor development. This fact has to promote special enzymological investigations having a goal to optimize anticancer therapeutic schemes including the PA metabolism modulators.
Leave a comment