Epigenetic mechanisms of the carcinogenic effects of xenobiotics and in vitro methods of their detection
Carcinogenesis is associated with various epigenetic mechanisms, which can alter intra- and intercellular communication and gene expression and thus affect cytokinetics, i.e. regulation of cell proliferation, differentiation, and apoptosis. These processes lead to a loss of homeostatic control. In addition to "classical" epigenetic events such as DNA methylation and histone acetylation, the major mechanisms include changes in concentrations of signal molecules (hormones, growth factors, fatty acids, etc.), modulation of cell receptors and drug-, hormone- and fatty acid-metabolizing enzymes, oxidative stress, and interference with intracellular signal transduction pathways. Multidisciplinary and multibiomarker approach is necessary for setting up a battery of specific biochemical, molecular, and cellular in vitro methods detecting the epigenetic carcinogenic potential of individual chemicals or their environmental mixtures. This approach is based on studies of modes of action of xenobiotics at various levels, including the molecular mechanisms and modulations of cytokinetics, each of them having its specific predictive value.