The theoretical generalization and a new solution to the scientific and applied problem in the field of genetics, optimisation of system analysis of the effectiveness of mutagenesis modifiers on the basis of which the laws of the influence of humic substances on spontaneous, induced chemical and radiation mutagenesis. A model system of complex analysis of qualitative and quantitative criteria for the evaluation of mutagenesis modification is developed, which increases the informativeness of cytogenetic and cytological analysis.
Humic substance has been shown to have antimutagenic properties under in vivo (in plant test-system) and in vitro (human lymphocyte culture) conditions, when combined with mutagenic factors (chemical mutagens) and upon action after exposure to mutagens (ionizing radiation), when exposed to the mutagen at the G0 stage (ionizing radiation), the G2 stage (dioxidine) and throughout the mitotic cycle, it is a medium-efficiency antimutagen with a wide range of continuous action.
It is shown that the investigated humic preparations exhibit antimutagenic properties in relation to the action of chemical mutagens with different mechanisms of action (prooxidant dioxidin, alkylating thiophosphamide and mitomycin C) and mutagenic efficiency. Integral indicators of antimutagenic efficacy of sodium humate in the Allium test have been determined. The antimutagenic effectiveness of sodium humate is increased in a number of mutagens: thiophosphamide (Kantimut = 0,47), mitomycin C (Kantimut= 0,30), dioxidine (Kantimut = 0,21).
The multiplicity of mechanisms of the gene-protective action of humic substances, which are manifested at the cellular and extracellular level, have desmutagenic and bioantimutagenic action, have been revealed.
It is proved that the studied humates exhibit properties of both therapeutic and prophylactic radioprotectors. Their modifying effect on radiation lesions is characterized by differential antimutagenic efficacy with respect to different types of aberrations, the most effective being the reduction of chromosomal type aberrations. The antimutagenic effects of humates are manifested in the concentration range of 10 μg / ml - 1000 μg/ml. At a concentration of 500 μg / ml, sodium humate exhibits mutagenic properties in human lymphocyte culture.
It is shown that the extracellular distribution of chromosome aberrations in the culture of human peripheral blood lymphocytes is best described by a compound Poisson and geometric distributions. The revealed differences in the nature of the cellular distribution of chromosome aberrations between the studied groups - the average group theoretically expected share of a subpopulation of cells with a geometric type of distribution (characterizing hidden chromosomal instability at the level of mechanisms of formation of aberrations) in the cell culture, 18,9% and 5,8% respectively. In individuals whose spontaneous mutagenesis has an individual theoretically expected proportion of cell subpopulation with a geometric type of subcellular aberration distribution ≥ 30%, the antimutagenic effect of sodium humate on radiation-induced mutagenesis is weak or absent.
The antimutagenic efficiency of sodium humate in the culture of peripheral blood lymphocytes of individuals without oncopathology and patients with thyroid cancer was found to be absent from rs13181 ERCC2 (Lys751Gln) and rs25487 XRCC1 (Gln399Arg) repair genes.
It is shown that sodium humate at a concentration of 100 μg / ml exhibits radioprotective properties in the culture of the L929 lineage cells. With a separate action of humate at this concentration, apoptosis is stimulated. At a concentration of 1000 μg / ml, toxic effects of sodium humate were detected in this test system.
It has been shown that sodium humate (1 μg/ml) exhibits radioprotective properties in primary culture of myogenic neonatal rat cells. The effect of sodium humate leads to stimulation of myogenic cell differentiation.
Key words: humic substances, mutagenesis, antimutagenesis, repair gene polymorphism.
