ABSTRACT
This chapter discusses the role of cell proliferation in carcinogenesis and the evidence suggesting an increased sensitivity of cells in early S phase to neoplastic transformation. In searching for the mechanisms that underlie this enhanced susceptibility of S-phase cells to chemical carcinogens, we have developed the following working hypothesis. The chapter focuses on mechanisms that are dependent on DNA replication. DNA replication follows a specific temporal order that is maintained from one cell generation to the next. This order is not necessarily the same among different cell types, and it has been documented that the timing of replication of certain genes is affected by their transcriptional activity and chromosomal location. The realization that cancer is basically a genetic disease, with both hereditary and somatic components, has provided a new framework for research in this field.
