Understanding Multi-Stage Carcinogenesis at the Molecular Level: Notes on Recent Progress

  • M. Hollstein
  • H. Yamasaki


While it is convenient to separate cancer stages into initiation and promotion phases, and to classify chemicals based on whether they have initiation or promoting activity, it is difficult to find mechanistic definitions that are internally consistent. A transforming point mutation in c-ras is experimentally inducible by an initiator, yet may occur either early or late in the development of cancer. Tumor promoters are considered non-genotoxic, yet TPA does affect the genome and can cause structural alterations in DNA. A further complication is that inducible cellular pathways can modulate DNA damage qualitatively and quantitatively. Basic research on the molecular biology of gene mutation, amplification, rearrangement, and transcription control in simple organisms that lend themselves to experimental manipulation, coupled with direct analysis of human tumors for genetic and other molecular changes will be useful in refining models of the critical steps in human cancer and the mechanisms by which they come about. Recent work on characterization of oncogenes, on gene transcription regulation, and on signal transduction pathways already has advanced our understanding considerably.


Acute Myeloid Leukemia Phorbol Ester Multistage Carcinogenesis Dihydrofolate Reductase Gene Mutagenic Carcinogen 
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Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • M. Hollstein
    • 1
  • H. Yamasaki
    • 1
  1. 1.International Agency for Research on CancerLyon cedex 08France

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