To understand the nature of interrelationships between carcinogenesis and DNA metabolism, chromosome structure, and biological reagents, in vivo and in vitro approaches are being used. Although carcinogenic agents have a variety of similar deleterious effects on hamster and human cells, only hamster cells transform to the malignant state in a regular, predictable fashion. The control mechanisms involving proliferation and growth control are obviously different. Evidence linking proto-oncogene expression with specific chromosome translocations has been obtained from studies involving Burkitt's lymphoma and chronic myeloid leukemia. Carcinogen treatment of human foreskin fibroblasts may result in structural chromosome alterations which frequently involve proto-oncogene loci. However, no cells that induce progressively growing tumors have resulted. Therefore, additional genetic alterations are required for complete expression of malignancy with indefinite proliferation. Oncogenes are being studied utilizing hamster and guinea pig malignant cells. Malignant guinea pig cell lines, independent of carcinogen treatment, but not their preneoplastic progenitor cells contain an activated oncogene. Therefore, the acquisition of oncogene activation appears closely associated with tumorgenicity. Furthermore, the activated oncogene is of a different type hitherto described. A new model involving transfection of human papilloma (HPV) DNA into both human and rodent cells with cocarcinogens is under study. Human cells with the papilloma-virus sequence have been obtained with a recombinant plasmid containing HPV 16. Transfection of this DNA into NIH 3T3 cells has resulted in a model for studying the molecular biology of viral DNA. Lastly, morphologic transformation and tumor production may be initiated by compounds which are not considered to be mutagens or to interact with DNA. Results with bisulfite indicate that qualitative polypeptide changes occur in the transition from the normal to the malignant state. Similar changes are seen as a result of malignancy induced by benzo-[a]-pyrene. Thus, a conversion of pathways responsible for carcinogenesis independent of the nature of initiation exists.
