The susceptibility of guinea pig cells to the colony-inhibitory activity of lymphotoxin during carcinogenesis.

The time of susceptibility of cells to lymphotoxin during carcinogenesis was determined. At different stages of in vitro chemical carcinogen-induced neoplastic transformation, colony formation of guinea pig cells was evaluated with lymphotoxin obtained from syngeneic nonimmune leukocytes. Cells exhibiting sequential morphological alteration, morphological transformation, and neoplastic transformation had been preserved in liquid nitrogen and, after reintroduction in culture, were analyzed simultaneously for their susceptibility to lymphotoxin. Morphologically altered and morphologically transformed cells at subcultures prior to neoplastic transformation were resistant to lymphotoxin inhibition of colony formation. Cells neoplastically transformed by N-methyl-N'-nitro-N-nitrosoguanidine in vitro or by N-methyl-N'-nitro-N-nitrosoguanidine or diethylnitrosamine with the host-mediated, in vivo-in vitro method were susceptible and exhibited a quantitatively culture-specific degree of colony inhibition. The parental noncloned and cloned neoplastically transformed cells in each series, furthermore, exhibited similar degrees of colony inhibition, which indicates that lymphotoxin susceptibility developed concomitant with, or close to, the time of neoplastic transformation and remained stable during subsequent cell generations.