Control of Cell Transformation, Mutagenesis, and Differentiation by Chemicals That Initiate or Promote Tumor Formation

摘要

Transformation of normal cells to malignant cells in vitro by chemical agents has been achieved in a number of fibroblastic and epithelial cell systems. The commonly used assays for cell transformation employ either diploid Syrian hamster embryo fibroblasts or cells from some permanent mouse and hamster fibroblast lines. Using an in vitro mammalian cell-mediated mutagenicity assay we were able to establish a relationship between the degree of mutagenesis in this assay, using mutable Chinese hamster V79 cells as target cells, and the degree of activity of carcinogens (initiators) in experimental animals. This assay also provided the means to study the organ specificity of chemical carcinogens. It is possible, however, that some environmental agents may act not as primary tumor initiating agents, but as tumor promoters, at a later stage of the carcinogenic process. Promoters cannot be detected with mutagenicity assays. In some cultured human melanoma and leukemia cells these tumor promoters, after binding to specific cellular receptors, induce the treated cells to differentiate into cells with characteristics of mature cells. This property of the tumor promoter to induce cell differentiation suggests that tumor promotion may, among other things, involve the expression of mutated tumor genes in a process similar to gene expression during cell differentiation. This paper discusses the usefulness of in vitro cell transformation, differentiation, and mutagenesis systems for studies of the mechanisms of carcinogenesis. (ERA citation 08:042393)