Nongenotoxic Mechanisms in Carcinogenesis: Role of Inhibited Intercellular Communication

摘要

Carcinogenesis is a multistep process, involving several distinct mechanisms, involving the conversion of a normal stem-like cell to a cell resistant to terminal differentiation (i.e., initiation), followed by the clonal expansion of this initiated cell (i.e., promotion), during which time additional changes occur allowing the cell to become malignant (i.e., progression). Each of these distinct operational stages of carcinogensis probably involves mechanisms (i.e., many mechanisms for initiation and promotion). Since gene and chromosomal mutations, cell death, and modulation of gene expression are the biological consequences of chemical exposure, many genetic, biological, and environmental factors can modulate how a given chemical can induce these changes. The general paradigm of 'carcinogenesis as mutagens' is considered totally inadequate to design the test protocol for animal bioassays and to interpret the data from these tests. The role of inhibited intercellular communication has been postulated to play a role in the tumor promotion and progression phases . Examination of experimental results of known tumor promotes as inhibitors of intercellular communication is presented. Implications of these results suggest a new paradigm is needed to approach the problem of a 'biological risk assessment' model. 'Science progresses more by the introduction of new world views or 'pictures' than by the steady accumulation of information.' Reprints. (AW)