Phenotypic Changes in Epithelial Cell Population Undergoing Neoplastic Transformation in Vitro

Abstract

Publisher Summary Explant cultures of F-344 rat tracheas exposed in vivo or in vitro to chemical carcinogens form established cell lines, whereas nonexposed tracheal explants do not. Many of these carcinogen-altered cell lines are not capable of forming tumors when inoculated into isologous, immunosuppressed rats, but they acquire this ability with repeated subculture in vitro . These altered cell populations are phenotypically distinguishable from normal populations on the basis of increased DNA contents by flow cytometry and by the appearance of a cell surface antigen. This chapter reviews changes in these markers that occur as carcinogen-altered nontumorigenic populations acquire the neoplastic phenotype in vitro . All carcinogen-altered cell lines examined in the chapter show increases in DNA values as compared to DNA contents of normal diploid tracheal cell populations. The transition from nontumorigenic to tumorigenic populations is also characterized by a change in relative DNA content in four of the five lines tested, which suggested the emergence of a new cell population. DNA histograms of neoplastic populations of cell lines 3F3 and 165D showed profiles indicative of mixed populations. In both cases, the smaller subpopulation had DNA profiles that corresponded to profiles obtained during the preneoplastic phase. Cloning of the neoplastic phase of cell line 3F3 confirmed the coexistence of two subpopulations and tumorigenicity studies confirmed that the minor cell subpopulations were the remnants of nontumorigenic preneoplastic cells.