Reverse transformation, genome exposure, and cancer

Publisher Summary This chapter reviews the new developments in the reverse transformation (redifferentiation) and the theoretical formulation of the role of genome exposure in cancer. The reverse transformation reaction of malignant cells is restored to a more normal phenotype. The change in morphology accompanying the reverse transformation of Chinese hamster ovary (CHO) cells is also demonstrated in the chapter. 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 as in normal cells. Various aspects of genome exposure around the nucleoli and the nuclear periphery are discussed in the chapter. The special role of the cytoskeleton in regulating exposure resulting in normal differentiation and malignant transformation is discussed in the chapter. An intact cytoskeleton is essential for the reverse transformation reaction, including the restoration of genome exposure. The action of the two-level system for regulation of the mammalian genome is reviewed in the chapter in relation to the normal differentiation and malignancy with indication of roles played by various metabolites, transcription factors, protooncogenes, cell organelles, and processes—such as specific phosphorylation and dephosphorylation. Possible implications for cancer therapy and prevention and for the fields of genetic disease and toxicology are described in the chapter.