Natural history of neoplastic development during hepatocarcinogenesis.
A diagrammatic depiction of the natural history of neoplastic development during hepatocarcinogenesis. The formation of an initiated cell following application of an initiating agent (complete or incomplete carcinogen), subsequent promotion by stimulated cell replication to an identifiable lesion (enzyme-altered focus), and subsequent conversion of the initiated cell progeny in the stage of promotion to the development (probably clonal) of the cells in the stage of progression. The effect of the removal of the promoting agent with subsequent cell death of the majority of cells in the stage of promotion, with retention of at least a "stem cell" for each focus, is also noted. The genetic alterations likely leading to initiation and to progression are noted as an asterisk for initiation (representing relatively small structural changes in the DNA) and by a clastogenic event as the hallmark of the stage of progression.