Cellular targets and host genes in multistage carcinogenesis.

Recent studies indicate that although cellular DNA is the critical target in the action of initiating carcinogens, specific membrane-associated receptors mediate the actions of certain tumor promoters. A stereochemical model is presented to explain how three different types of tumor promoters (phorbol esters, indole alkaloids, and polyacetates) can interact with the same class of cellular receptors. Multistage chemical carcinogenesis might involve progressive alterations in the expression of cellular DNA sequences homologous to oncogenes and regulatory sequences in certain retroviruses. We found that the oncogene c-mos is not rearranged or expressed in a series of carcinogen-transformed murine C3H 10T112 cells. These cells do express, however, a unique set of poly(A)+ RNAs that contain sequences homologous to the Moloney leukemia virus long terminal repeat sequence. Studies are in progress to determine the significance of this finding with respect to the carcinogenic process.