Reverse transformation, genome exposure, and cancer

The reverse transformation reaction whereby malignant cells are restored to a more normal phenotype has been reviewed. The primary causative action is ascribed to the genome exposure reaction in which a peripheral nuclear DNA region is restored to high sensitivity to DNase I, like that in normal cells. Various aspects of genome exposure around the nucleoli and the nuclear periphery are considered. The special role of the cytoskeleton in regulating exposure resulting in normal differentiation on the one hand and malignant transformation on the other is discussed. The action of the two-level system for regulation of the mammalian genome previously proposed is reviewed in relation to normal differentiation and malignancy with brief indication of roles played by various metabolites, transcription factors, protooncogenes, cell organelles, and processes like specific phosphorylation and dephosphorylation. Possible implications for cancer therapy and prevention and for the fields of genetic disease and toxicology are indicated.