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Multi-stage chemical carcinogenesis in mouse skin: Fundamentals and applications

Nature Protocols volume 4, pages 1350–1362 (2009)Cite this article

Abstract

For more than 60 years, the chemical induction of tumors in mouse skin has been used to study mechanisms of epithelial carcinogenesis and evaluate modifying factors. In the traditional two-stage skin carcinogenesis model, the initiation phase is accomplished by the application of a sub-carcinogenic dose of a carcinogen. Subsequently, tumor development is elicited by repeated treatment with a tumor-promoting agent. The initiation protocol can be completed within 1–3 h depending on the number of mice used; whereas the promotion phase requires twice weekly treatments (1–2 h) and once weekly tumor palpation (1–2 h) for the duration of the study. Using the protocol described here, a highly reproducible papilloma burden is expected within 10–20 weeks with progression of a portion of the tumors to squamous cell carcinomas within 20–50 weeks. In contrast to complete skin carcinogenesis, the two-stage model allows for greater yield of premalignant lesions, as well as separation of the initiation and promotion phases.

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Figure 1: Two-stage model of skin carcinogenesis in mice.
Figure 2: Expression of several marker proteins in each sequential stage of skin carcinogenesis in mice.
Figure 3: Representative data from a two-stage skin carcinogenesis study in FVB mice.

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Acknowledgements

This work was supported by NIH grants ES015718, ES016623, CA076520, CA37111, CA016672 and the National Institute of Environmental Health Sciences Center Grant ES007784. We would like to thank the Histology and Tissue Processing Core Facility for their technical assistance in immunohistochemical analyses and Dr. J. Rundhaug for providing tumor samples. We also thank S. Johnson for her assistance in the preparation of this manuscript.

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  1. Department of Carcinogenesis, Science Park-Research Division, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas, USA

    Erika L Abel, Joe M Angel, Kaoru Kiguchi & John DiGiovanni

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  1. Erika L Abel
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  2. Joe M Angel
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  3. Kaoru Kiguchi
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Contributions

E.L.A. and J.D. were responsible for overall manuscript writing including compilation of the supporting data and procedure descriptions. J.M.A. was responsible for compiling and describing the data in Table 1. K.K. was responsible for creating and describing the results of Figure 2. Numerous laboratory groups and individuals have contributed to the design and refinement of the two-stage skin carcinogenesis protocol in mice.

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Correspondence to John DiGiovanni.

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Abel, E., Angel, J., Kiguchi, K. et al. Multi-stage chemical carcinogenesis in mouse skin: Fundamentals and applications. Nat Protoc 4, 1350–1362 (2009). https://doi.org/10.1038/nprot.2009.120

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