Differentiating among proposed mechanisms for tumor promotion in mouse skin with the use of the multievent model for cancer.
Numerous mechanisms for tumor promotion in mouse skin have been recently proposed. These include the multistage, genetic view of Slaga, Furstenberger, and Marks; the multistage, genetic and/or epigenetic view of Parkinson; and the two-stage view of Yuspa and Hennings. With the use of the multievent model, a mathematical model for cancer that can incorporate cell proliferation phenomena, these tumor promotion mechanisms were modeled mathematically. It was found that the models had different predictions about the incidence of papillomas in initiator-promoter-initiator experiments and the incidence of carcinomas in initiator-promoter experiments with varying periods of tumor promotion. Upon analysis, existing data were shown to be in agreement with the Yuspa and Hennings two-stage model. The analysis also supported the view, formulated by Scribner and co-workers, that different types of initiated cells were created, some capable of transformation to carcinomas and some not. Phenomena determined by use of benign tumors as the end point may need to be demonstrated with the use of the carcinoma as the end point, prior to the acceptance of these phenomena being applicable to the human carcinogenic process.
D015112:4-Nitroquinoline-1-oxide; D000096:Acetone; D000818:Animals; D002471:Cell Transformation, Neoplastic; D008433:Mathematics; D051379:Mice; D008954:Models, Biological; D010212:Papilloma / Q000139:chemically induced / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate; D014520:Urethane
D000096:Acetone; D014520:Urethane; D015112:4-Nitroquinoline-1-oxide; D013755:Tetradecanoylphorbol Acetate