| Abstracts: For almost a century now, the view that carcinogenesis takes place at the cellular and subcellular levels of biological complexity has been the prevalent one. The implicit premises of this hypothesis, called the Somatic Mutation Theory are: 1) cancer originates within a single cell; 2) carcinogens generate stable mutations in the DNA of the cell that will eventually become a tumor cell, and 3) these mutations increase the proliferative rate of the neoplastic cell. Another tacit premise of this theory is that the default state of cells in metazoa is quiescence. Alternatively, epigenetic mechanisms similar to those occurring during histogenesis and organogenesis have been proposed to be at the core of carcinogenesis. During early development in metazoa, the interaction between stroma and epithelium in 3morphogenetic fields2 exert instructive influences on each other resulting in normal organ formation. These 3morphogenetic fields,2 three-dimensional structures that carry positional and historical information, are units of tissue organization and maintenance that remain active throughout the lifetime of the individual. Cancer appears as a response to a complex, abnormal tissue environment. Thus, studying tissues 3in context2 offer a chance to understand the multi-directional pathways that connect those tissues, cellular microenvironments and the genome, and identify why these interactions may become altered under the effect of carcinogens. Based on this evidence and applying an evolutionary perspective to the subject of control of cell proliferation (proliferation is the default state of cells in metazoa), we have postulated the Tissue Organization Field Theory of carcinogenesis. Briefly, this theory posits that the objective target of carcinogens are tissues. The role of carcinogens is to disrupt the normal flow of information between the stroma and the parenchyma and/or among cells within those tissues that maintain the normal tissue phenotype. | (traduction française en construction) |
