[Mutational-metabolic model of carcinogenesis and the progression of the neoplastic process].

The given data indicate the presence of a negative correlation between metabolic indices (a decrease of the tolerance to glucose, increase of the blood level of free fatty acids, insulin, cholesterol triglycerides, cortisol, stc) and the indices of cellular immunity, which is determined by the number of rosette-forming cells and blasttransformation reaction to PHA and skin tests. Accordingly, the administration of an antidiabetic drug-phenformin (phenetylbiguanide)--apart from the improvement of metabolic pattern, results in the restoration of the cell-mediated immunity indices. These findings provide a basis for stating the phenomenon of metabolic immunodepression. The metabolic immunodepression may be supposed to prevent immunological surveillance activation, which normally is realized through the signals, provided by cells subjected to somatic mutation. It is noteworthy that the given metabolic conditions (hypercholesterinemia, hyperinsulinemia, the enhanced utilization of free fatty acids) promote the division of somatic cells. Thus, the same metabolic shifts which increase the pull of proliferating cells and, accordingly, increase the possibility of mutation development, also cause the metabolic immunodepression at the same time. These opposite metabolic influences on somatic cells and T-dependent lymphocytes cause the development of the syndrome of cancrophilia. The syndrome of cancrophilia normally arises at pregnancy, in intensive growth of the organism in childhood, accelerated development, stress and during normal ageing. Many carcinogens cause the decrease of tolerance to glucose, the increase in blood-insulin level and elevation of the threshold of sensitivity of the hypothalamus to feedback suppression. This phenomenon is based on the decrease of catecholamine level in thehypothalamus in ageing, stress and the action of some carcinogens. Thus, the syndrome of cacrophilia provides the conditions for cancer development and tumor progression, besides, the tumor itself produces the metabolic shifts typical of cancrophilia. In the light of mutation-metabolic model of cancer development, it is possible to consider the fundamental factors which increase of hinder carcinogenesis.