Progress Report on Induction of Transformations in Cultured Epithelial Cells, 8-1-78 to 5-31-79

摘要

During the report period the induction of morphologic transformation in both murine and human epithelial lung cultures was studied. The results of the first dose-response curve study showed a dose dependent increase in the yield of transformants versus methylcholanthrene concentration through 5 ug/ml followed by a decline in yield at 10 ug/ml. These curves are in terms of transformants per cell exposed and therefore fit with conventional wisdom, i.e., the rising arm of the curve reflects an increase in transformants with dose, while the descending arm reflects the counterbalancing effects of cytotoxicity. Attempts to repeat this curve consistently failed. By sequentially removing each of the additives, it was learned that it was necessary to have high levels of hydrocortisone present during carcinogen exposure in order to obtain successful morphologic transformation. A repeatable assay for morphologic transformation of epithelial lung cells is now established. Two human lung samples have been studied in essentially the same system. Of the three transformed human lines studied thusfar, all have grown to form colonies in soft agar, and all have formed multicellular tumor speroids. The relationship between the morphologic transformant and the cells which give rise to soft agar collonies, multicellular tumor spheroids and, hopefully, tumors is problematic. The solution awaits a clonal isolation technique for the transformants. (ERA citation 07:051808)