Response modification in carcinogenesis.
A major goal in multistep carcinogenesis research is the integration of recent findings obtained by sophisticated molecular-genetic and cytogenetic analysis of cancer into the more descriptive concepts of experimental pathology. It is proposed that the creation of a promotable cell in carcinogenic initiation requires a response modification to extracellular or intercellular signals. Different types of response modification can be distinguished: changes in the receptors for growth and differentiation factors and their cytoplasmic and nuclear signal transduction pathways; increased resistance of initiated cells to cytotoxic agents; alterations in junctional cell-to-cell communications. The challenge of a response-modified cell to an appropriate promoter results in its selection and clonal expansion, usually to a benign tumor. In addition, for malignancy, chromosomal changes are required that affect cellular functions that can play a role early or late in tumorigenesis. These concepts are illustrated with examples from oncogene research and oxidant promotion.
Cerutti
P A
PA
Department of Carcinogenesis, Swiss Institute for Experimental Cancer Research, Epalinges/Lausanne.
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D051379:Mice; D009857:Oncogenes / Q000187:drug effects*; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced
D002273:Carcinogens