EPIGENETIC MECHANISMS OF THE CANCEROGENESIS

The biological activity of many cancerogenic agents is manifested in genotoxicmechanisms by changing the information encoded in the DNA molecules.However, it becomes much clearer that there are non-genotoxic (epigenetic) cancerogenswhose action is manifested trough changes of the genes activity withoutcausing mutations. The transformation of the normal cell into a malign one requires agreater number of genetic and/or epigenetic changes that undergo at least threephases, namely, initiation, promotion and progression. The epigenetic cancerogenes realize their effect primarily in the promotion phase, primarily, by stimulating the celldivision (mitogenesis). Unlike the genotoxic agents affecting the DNA molecule, thenon-genotoxic cancerogenes can affect a considerably greater number of cellconstituents and products, that is, the components of the signal transduction system,the protein factors involved in the regulation of replication, reparation andtranscription of the DNA. Besides, the non-genotoxic cancerogenes can change adegree of methylation of the nucleus DNA and chromatin confonnation. Despiteprominent differences between the genotoxic and the non-genotoxic cancerogenes, itis necessary to stress that such a way of division is somewhat imprecise regarding thefact that the chemical cancerogenes often exert their effect through a combination ofmechanisms while the primary mechanisms of effect can vary depending on the typeof the cell.