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Gennady A. Savostyanov

Despite of considerable effort and invest made in molecular biology research, there is no notable breakthrough in carcinogenesis mechanisms understanding. It must be substantial reasons to account for this situation, and one of them could be incorrect general direction of investigation. At present, investigation of cell differentiation and growth mechanisms are in the focus of attention. Meanwhile, we believe that the change of cell arrangement and communication rather that cell itself plays a crucial role in normal morphogenesis of epithelial sheets and carcinogenesis.

The present conception of tissue structure is known to be based on the study of thin and, practically, 2 - dimensional tissue sections. However, 3 - dimensional structure of normal and pathological tissues is poorly studied and its reconstruction is pretty complex. Hence a new approach to the investigation of 3 - dimensional shape and spatial arrangement of cells in epithelial sheets is developed.

The approach is based on an assumption that tissues consist of cell groups rather that cells itself. These groups are originated due to the division of functions between cells and represent the elementary units of the tissues. Limited conditions for possible kinds of division of functions are found, and classification of cell groups is proposed as a periodical low. These groups or units represent an overlooked level of biological organization that situated between cell's and tissue's levels. Therefore one may consider tissues as polymeric units.

There are natural set of rules for units polymerization. So the periodic cell mosaics with translational symmetry should be typical to epithelia. It is important to emphasize that number of all possible variants of such mosaics are limited and can be calculated. These mosaics can have "chromatic" variants. The mosaic's parameters are new and worthy markers of tissue structure.

According to this hypothesis, theoretical evidences that as many as 11 topological variants of cells arrangement (cell mosaic patterns) are available for simple epithelium instead of a single one suggested so far, were found. All these mosaics are known in mathematics as Kepler's regular parquets and characterized by the translation symmetry. The mosaics limits directions of epithelia development in onto- and phylogenesis. So the prediction of the tissue development is possible.

Up to now 8 variants of such epithelial mosaics in different animals have been already found experimentally. The discovery of other ones is possible in future. Also, some of them may appear in the future evolution of multi-cell organisms.

The results enable us to initiate the study both topological and metrical aspects of spatial organization of stratified epithelia and to determine the nature and biological reasons of their symmetry.

According to the results a model of 3 - dimensional shape and spatial arrangement of cells in pseudostratified epithelial sheets were developed. Preliminary data seem to confirm the models and indicate the importance of the investigation.

The present investigation brings us to the conclusion that tissue topology transformation during carcinogenesis one may be compared with phase transformation in physics and described quite accurately. The analysis of transformation of cell mosaics symmetry may provide the key for understanding of carcinogenesis and the role of tissue elemental units in these processes.

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