Carcinogenesis clonal models

Zielinski, J. M., Kodell, R. L., and Krewski, D. (2001). Interaction between two carcinogens in the two-stage clonal expansion model of carcinogenesis. J Epidemiol Biostat 6, 219-228. 

Figure 3 A Four-Stage Model of Carcinogenesis With Clonal Expansion and Repair...

The mechanism of action of drug induced hepatocellular tumors is quite similar to epidermal carcinogenesis. There are a series of biochemical changes such as enzyme induction that are parallel in liver and skin. Hyperplastic nodules result from promoter treatment and these nodules regress if the promoting stimulus is removed up to a critical point, after which the nodule is committed to develop into a hepatoma. The preneoplasic nodules contain enzyme altered foci for y-glutamyltranspeptidase, canalicular ATPase, glu-cose-6-phosphatase and iron deficient foci (Pitot et al., 1982). It is not clear whether or not all of the enzyme alTered foci result in hepatomas but they are certainly direct evidence of enhanced clonal growth or cell section and proliferation of presumably initiated cells. The promotional model can be modified by hormonal and dietary factors and this model has potential use for extrapolation to the human population. 

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