It takes a tissue to make a tumor: Epigenetics, cancer and the microenvironment

How do normal tissues limit the development of cancer? This review discusse s the evidence that normal cells effectively restrict malignant behavior, a nd that such tissue forces must be subjugated to establish a tumor. The act ion of ionizing radiation will be specifically discussed regarding the disr uption of the microenvironment that promotes the transition from preneoplas tic to neoplastic growth. Unlike the highly unpredictable nature of genetic mutations, the response of normal cells to radiation damage follows an epi genetic program similar to wound healing and other damage responses. Our hy pothesis is that the persistent disruption of the microenvironment in irrad iated tissue compromises its ability to suppress carcinogenesis.