Pryzymyrska T. Role of hyperhomocysteinemia in the dynamics of malignant tumour growth (an experimental study).

The object is 790 laboratory animals with experimental hyperhomocysteinemia (HHCy) and experimental tumors; the aim - to establish a role of HHCy in dynamics of growth of malignant tumours and experimentally to prove necessity of its correction at growth of malignant tumours; methods are methods of experimental biology and oncology in vivo, histological, immune-enzyme analysis, chromatographic, molecular, and statistic; novelty - a new methionine vitamin-deficiency model of HHCy is created; it is shown that growth of malignant tumours is accompanied the increase of HCy concentration in plasma of blood of animals at the stage of exponential tumour growth and by a decline - in the terminal stage of their growth. It is set that the increase of HCy concentration in the blood plasma of laboratory animals correlates directly with the age of animals and the decrease of the level of general tissue-specific DNA methylation. It is shown that at the terms of HHCy is negatively modified a carcinogenic effect of N-methyl-N-nitrosourea (NMU) on tissue of the mammary gland of rats (the decrease of latent period and the increase of relative quantity, mass, and volume of mammary malignant tumours). It is set that at experimental HHCy are the deceleration of the growth and metastasis of transplanted tumours, the intensification of the processes of tumour vessel obstruction, and the considerable decrease of the anti-tumour effect of doxorubicine. It is shown that the complex of vitamins of В6, В9 and В12 normalizes the HCy concentration in the blood plasma. It also protects from the total DNA hypomethylation in the liver and the tumour, degrades the HHCy effects on the NMU-induced mammary rat carcinogenesis, counteracts to the decrease of the antitumour effect of doxorubicine, and did not promote the tumour growth. The obtained results may be introduced is to the practice of oncological clinics for the correction of HHCy at oncologic patients, that would be advantageous for the increase of efficiency of doxorubicine at theirtreatment.