Apoptosis in Carcinogenesis: The Role of p53

Abstract

In this paper, we explore the role played by apoptosis in the genesis of cancer. The hypothesis under test is that apoptosis affords a means whereby cells that have sustained genotoxic damage can be irreversibly deleted from the generative compartment of the affected tissue. Such damaged cells might otherwise have acquired serious but survivable DNA modifications, and so could have become the precursors of malignant clones (Fig. 1). One means of testing the hypothesis is to devise systems in which a critical gene on the signaling pathway from genotoxic damage to apoptosis is selectively disabled. Following exposure to the genotoxic agent, cells bearing such disabled genes would be expected to survive, generating a population of previously "forbidden" cells. The hypothesis predicts that these cells should have undergone genomic changes similar or identical to those known to be clonally expanded in cancer, a proposition that can be addressed directly.