Initiation-promotion model

Figure 12.11 Initiation/promotion model. X = application of initiator, P = application of promoter.

TABLE 27.11 Critical review of in vivo initiation-promotion model systems for identification and characterization of atypical tumor promoters and tumor progression... 

Figure 24.15. Diagrammatic scheme of the initiation promotion model. Topical application of a subthreshold dose of an initiating carcinogen to mouse skin will result in no tumor formation however, if this dose is followed by repetitive treatment with a tumor promoter, then tumors will develop. Initiation is an irreversible genetic event leading to the development of an initiated cell which can remain dormant until exposed to a tumor promoter. Tumor promoters produce the clonal expansion of the initiated cell to form a tumor.

In the rodent liver initiation-promotion model, phenobarbital is a tumor promoter. Phenobarbital is a hepatic mitogen, and recent evidence indicates that it activates the transcription factor, constitutive androstane nuclear receptor (CAR). Additionally, CAR was found to be essential for liver tumor promotion in pheno-barbital-treated mice. In phenobarbital promoted preneoplastic foci and hepatic tumors, phenobarbital can also suppress apoptosis and accelerate the growth of the foci or tumor. Withdrawal of phenobarbital treatment is accompanied by an increase in apoptosis. Similar results involving the inhibition of apoptosis have been reported for nafenopin, a peroxisome proliferator and hepatic tumor promoter. 

Neonatal rodents (in vivo) Initiation-Promotion models (in vivo)... 

Burns, R, Albert, R., Altshuler, B., and Morris, E. (1983). Approach to risk assessment for genotoxic carcinogens based on data from the mouse skin initiation-promotion model. Environ Health Perspect 50, 309-320. 

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