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SUMMARY 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.

CELLS derived from several animal species, including mouse1,2, hamster3 and rat4, have been transformed in vitro from the normal to the malignant state by diverse chemical carcinogens. In similar conditions, however, attempts to transform human cells have usually been unsuccessful and as far as we know, such transformation has been reported only once5. This was a case of two cell lines treated with urethane, obtained from siblings with von Recklinghausen's disease, a familial disorder transmitted by an autosomal dominant gene, and characterised by multiple fibromas with a high predisposition to malignant transformation in vivo6. Although morphologically altered foci of transformed cells were reported, there was the possibility that a few tumour cells in the original population had been selected for by urethane. Therefore we characterised in detail the urethane-treated and untreated cultures. We have found that human cells can indeed be chemically transformed in vitro.