Genetic Instability Occurs Sooner Than Expected: Promotion, Progression and Clonality During Hepatocarcinogenesis in the Rat

  • Oscar Sudilovsky
  • Lucila I. Hinrichsen
  • Tom K. Hei
  • Cecilia M. Whitacre
  • Jian H. Wang
  • Sriram Kasturi
  • Shi H. Jiang
  • Ronald Cechner
  • Stella Miron
  • Fadi Abdul-Karim
Part of the Basic Life Sciences book series (BLSC, volume 57)


The basic question of “at which point in time does genetic instability occur in the natural history of cancer” can be answered only with another question: in which organ or model? Dr. Shapiro has just given us an impressive account of her work in human malignant gliomas. We also attempted to explore the problem but in a different organ, species and model system. We found that in the rat liver treated with diethylnitrosamine (DEN) and a choline deficient (CD) diet, genomic instability expressed by aneuploidy takes place during the promotion treatment, long before hepatocarcinomas can be diagnosed (1, 2). The presence of aneuploidy implies that irreversible genetic changes, characteristic of progression, occur during dietary promotion (Fig. 1). Since increasing evidence points out that most malignant hepatomas are monoclonal in origin, this fact and the studies previously mentioned have led us to propose now a scheme of cell renewal which explains the overlapping of promotion with progression arising in the clonally replicating foci of preneoplastic populations.


Individual Focus Aneuploid Cell Liver Carcinogenesis Clonal Nature Choline Deficient 


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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Oscar Sudilovsky
    • 1
  • Lucila I. Hinrichsen
    • 1
  • Tom K. Hei
    • 1
  • Cecilia M. Whitacre
    • 1
  • Jian H. Wang
    • 1
  • Sriram Kasturi
    • 1
  • Shi H. Jiang
    • 1
  • Ronald Cechner
    • 1
  • Stella Miron
    • 1
  • Fadi Abdul-Karim
    • 1
  1. 1.Institute of PathologyCase Western Reserve UniversityClevelandUSA

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