Molecular Toxicology of Chromatin: The Role of Poly (ADP-Ribose) in Gene Control
Final rept. Jan-Dec 1985
CALIFORNIA UNIV SAN FRANCISCO CARDIOVASCULAR RESEARCH INST
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This research endeavor approaches chromatin toxicity in a selective manner. Environmental factors both physical and chemical exert a subtle long- term effect on cellular systems, that is distinguishable from the acute lethal effects of toxins or high doses of radiation. We focus our attention on the effect of low-dose toxicology which affects cellular behavior and alters cellular phenotype. Present concepts define the molecular basis of cellular phenotype as a carefully and specifically orchestrated composite of gene- expressions, which contain both the determinants of cellular phenotype and life expectancies of specific cell types. Notably, chemical or radiation effects will inevitably result in cellulary phenotypic chages, the most pervasive being malignancy. The specific experimental approach commenced with the study of the nuclear polymer ADP-riboseN, which we predicted could lead to a more basic understanding of gene regulations proto-oncogene and differentiation regulation being the defined field. Keywords Antitransformation.