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 a ffect cytokinetics, i.e. regulation of cell proliferation, differentiation, and apoptosis. These processes lead to a loss of homeostatic control. In a ddition to "classical" epigenetic events such as DNA methylation and histon e acetylation, the major mechanisms include changes in concentrations of si gnal molecules (hormones, growth factors, fatty acids, etc.), modulation of cell receptors and drug-, hormone- and fatty acid-metabolizing enzymes, ox idative stress, and interference with intracellular signal transduction pat hways. Multidisciplinary and multibiomarker approach is necessary for setti ng up a battery of specific biochemical, molecular, and cellular in vitro m ethods detecting the epigenetic carcinogenic potential of individual chemic als or their environmental mixtures. This approach is based on studies of m odes of action of xenobiotics at various levels, including the molecular me chanisms and modulations of cytokinetics, each of them having its specific predictive value.