ABSTRACT

Transformation of human cells in vitro by any of several different carcinogens induces a sequence of phenotypic changes which ultimately results in the expression of a neoplastic phenotype. Many of the similarities between in vitro transformed human epithelial cells and fibroblasts are presented in addition to comparisons between carcinogen-treated normal cells and their normal cell counterparts or spontaneous human tumor cells. Many carcinogen-treated human skin fibroblast cells exhibit anchorage-independent growth after the cells are treated with different concentrations of carcinogens, but do not form progressively growing tumors. Cytotoxicity on isogenic fibroblasts was determined to select a noncytotoxic dose to use for transforming keratinocytes. The chapter presents the induced mutation frequency of cells treated with human S9-activated Benzo(a)pyrene. In contrast to other experiments with other mutagens, strict dose-dependent increases in mutatin responses did not appear when compared to increases in the cytotoxicity of the compound of interest.