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Interruption of cell transformation and cancer formation

Maurice S. Fox^*,1 and Sidney Klawansky

^* Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; and

Department of Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts, USA

¹Correspondence: Department of Biology, Rm. 68–577a, M.I.T. Cambridge, MA 02139, USA. E-mail: msfox{at}mit.edu

A review of the results of X-ray and chemical carcinogen induction of transformation of mouse cells supports a two-step epigenetic model of transformation. According to this model, exposure induces an epigenetic regulatory alteration that makes the cells hypermutable so that when the cell population inheriting this alteration becomes sufficiently large, the second step, a mutation to the transformant phenotype, becomes increasingly likely. The epigenetic alteration in X-ray-exposed mouse cells has been demonstrated to be reversible by brief exposure to certain protease inhibitors. If the rodent cell experiments constitute a valid system for studying human cancer, then this two-step model may herald rich opportunities for preventing and perhaps even treating cancer in humans.—Fox, M. S., Klawansky, S. Interruption of cell transformation and cancer formation.

Key Words: epigenetics • carcinogenesis • hypermutability • genetic regulation • prevention

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