ABSTRACT
Clinical investigations have shown a correlation between the number of positive nodes in certain human tumor patients and the existence of amplified oncogenes in tumor cells. DNA amplification occurs physiologically in normal cell regulation and differentiation and is also the result of genotoxic insult. The influence of differentiation on the ability of a cell to amplify a specific DNA sequence has been studied in F9 mouse teratocarcinoma stem cells. The binding of one or more cellular factors to the early domain is absolutely necessary as the initial step in the process of DNA amplification. The existence of a transacting cellular factor was confirmed by cell fusion experiments between irradiated or carcinogen-treated cells and untreated cells carrying the indicator gene. Immortalized cell lines and tumor cells may have regained the stem-cell property rendering them amplification proficient. Cycloheximide could cause cellular deprivation of a labile regulator affecting transcriptional rate, mRNA half-life, or translation. Carcinogens might act through another mechanism.
