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Open Access Heterogeneity of the Tumorigenic Phenotype Expressed by Madin–Darby Canine Kidney Cells

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Abstract:

The mechanisms by which cells spontaneously immortalized in tissue culture develop the capacity to form tumors in vivo likely embody fundamental processes in neoplastic development. The evolution of Madin–Darby canine kidney (MDCK) cells from presumptively normal kidney cells to immortalized cells that become tumorigenic represents an example of neoplastic development in vitro. Studies of the mechanisms by which spontaneously immortalized cells develop the capacity to form tumors would benefit from quantitative in vivo assays. Most mechanistic correlations are evaluated by using single-dose tumor-induction experiments, which indicate only whether cells are or are not tumorigenic. Here we used quantitative tumorigenicity assays to measure dose-and time-dependent tumor development in nude mice of 3 lots of unmodified MDCK cells. The results revealed lot-to-lot variations in the tumorigenicity of MDCK cells, which were reflected by their tumor-inducing efficiency (threshold cell dose represented by mean tumor-producing dose; log10 50% endpoints of 5.2 for vial 1 and 4.4 for vial 2, and a tumor-producing dose of 5.8 for vial 3) and mean tumor latency (vial 1,6.6 wk; vial 2,2.9 wk; and vial 3,3.8 wk). These studies provide a reference for further characterization of the MDCK cell neoplastic phenotype and may be useful in delineating aspects of neoplastic development in vitro that determine tumor-forming capacity. Such data also are useful when considering MDCK cells as a reagent for vaccine manufacture.

Document Type: Research Article

Affiliations: 1: Division of Viral Products, Office of Vaccines Research and Review, University of Illinois at Chicago, Chicago, Illinois, USA 2: Division of Veterinary Services, Center for Biologics Evaluation and Research, Food and Drug Administration, University of Illinois at Chicago, Chicago, Illinois, USA 3: Division of Veterinary Resources, National Institutes of Health, Bethesda, Maryland, USA 4: Section of Infectious Diseases, Immunology and International Medicine, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 5: Division of Viral Products, Office of Vaccines Research and Review, University of Illinois at Chicago, Chicago, Illinois, USA. andrew.lewis@fda.hhs.gov

Publication date: June 1, 2011

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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