Induction of Unusual Tumors in Vivo by Rat Fibroblasts Treated with Diepoxybutane

Diploid rat embryo fibroblasts exposed to diepoxybutane, a carcinogenic alkylating agent, exhibited chromosome aberrations and a high proportion of tetraploid cells immediately after treatment. Following a prolonged period of carcinogen-free growth, a diepoxybutane-treated cuture showed morphologic transformation and produced transplantable malignant tumors upon inoculation into neonatal rats. Morphologic and histochemical characteristics of the tumors derived from cells exposed to diepoxybutane in culture were also found in tumors of animals exposed directly to this carcinogen. The tumors from diepoxybutane-treated cell cultures were composed of highly anaplastic giant cells with centrally located cytoplasmic inclusions. Clusters of identical cells were found in some of the tumors obtained by direct in vivo treatment of rats with diepoxybutane. The morphologic similarities of these tumors suggest that similar processes of cellular evolution to malignancy occur in cell culture systems and in vivo.