I. In Vitrol Transformation of Rat Embryo Cells: Correlations with the Known Tumorigenic Activities of Chemicals in Rodents

Susceptibility to chemically induced transformation changed as a rat embryo cell culture was passaged. For the first 35 to 60 passages, the cultures were diploid and resistant to transformation by chemical carcinogens. However, cultures infected with a murine leukemia virus were transformed by chemicals. For the next 60 passages, the cultures were heteroploid, but retained contact inhibition and were not tumorigenic. Even without addition of heterotypic viruses, these heteroploid cultures could be transformed by chemicals, but the endogenous rat C-type virus could be demonstrated in the transformed cultures. At higher passages, the rates of spontaneous transformation gradually increased so that the cultures could not be used for transformation studies. Chemically induced transformation of the stable heteroploid cell line (F1706) was manifested by an easy to read focal alteration. Initial observations based on these foci were confirmed by inoculating the morphologically altered cells into isogeneic newborn rats. A number of carcinogenic and noncarcinogenic chemical analogues were tested for their ability to transform F1706 cultures. The compounds tested included 4 azo dyes, 12 polycyclic hydrocarbons, 12 aromatic amines, and 7 miscellaneous compounds. Based on the known activities of the same chemicals in rodents, certain active compounds failed to induce transformation in any test, and others induced transformation in only some tests, but these in vitro tests, if used as a screening assay, would have been correct in 82% of all individual tests, and over-all, would have correctly predicated the carcinogenic activity of 33 of the 35 agents tested.