Cellular targets and host genes in multistage carcinogenesis.

Area of Science:

• Molecular Biology
• Cancer Research
• Biochemistry

Background:

• Cellular DNA is the primary target of initiating carcinogens.
• Specific membrane receptors mediate tumor promoter actions.
• Multistage chemical carcinogenesis involves alterations in DNA sequences related to oncogenes and retroviruses.

Purpose of the Study:

• To present a stereochemical model for tumor promoter-receptor interactions.
• To investigate oncogene expression in carcinogen-transformed cells.
• To identify unique RNA sequences in transformed cells and assess their significance in carcinogenesis.

Main Methods:

• Development of a stereochemical model for tumor promoter interactions.
• Analysis of oncogene (c-mos) rearrangement and expression in murine C3H 10T112 cells.
• Characterization of poly(A)+ RNA sequences in carcinogen-transformed cells.

Main Results:

• A model explaining the interaction of phorbol esters, indole alkaloids, and polyacetates with cellular receptors was proposed.
• The oncogene c-mos was neither rearranged nor expressed in the studied carcinogen-transformed cells.
• Transformed cells expressed unique poly(A)+ RNAs with sequences homologous to the Moloney leukemia virus long terminal repeat.

Conclusions:

• Tumor promoters can interact with a common class of cellular receptors via specific stereochemical interactions.
• The expression of unique retroviral-like RNA sequences in transformed cells may play a role in the carcinogenic process.
• Further studies are needed to elucidate the precise significance of these RNA sequences in multistage chemical carcinogenesis.