The use of in vitro assays for neoplastic transformation and tumor promotion.

We investigated growth control in mixed cultures of normal and oncogene-transformed mouse fibroblasts. NIH/3T3 transformed by v-myc, polyoma large T, polyoma middle T, v-ras and v-src showed comparable cloning efficiencies in agarized medium. However, when cultivated with an excess of normal cells (Balb/3T3, C3H10T1/2 or primary rat and hamster embryo cells) ras, src, and middle T-transformed cells were able to form "foci" of transformation on the layer of density arrested normal cells, whereas myc- and polyoma large T-transformed cells lacked this ability. Addition of the phorbol ester tumor promoter, phorbol-12,13-didecanoate, rescued proliferation and focus-formation by these nuclear oncogenes-transformed cell lines. Evidence is presented and discussed supporting a main role of intercellular communication between normal and transformed cells in modulating suppression or expression of the transformed phenotype.