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Open Access Failure-to-Thrive Syndrome Associated with Tumor Formation by Madin–Darby Canine Kidney Cells in Newborn Nude Mice

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Abstract:

Tumors that formed in newborn nude mice that were inoculated with 107 Madin–Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 102.8 to 107.5); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor–derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases.

Document Type: Research Article

Affiliations: 1: Division of Veterinary Resources, National Institutes of Health, Bethesda, Maryland, USA 2: Division of Viral Products, Office of Vaccines, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, Maryland, USA 3: Division of Veterinary Services, CBER, Food and Drug Administration, Bethesda, Maryland, USA 4: Division of Veterinary Services, CBER, Food and Drug Administration, Bethesda, Maryland, USA; Office of Counter-Terrorism and Emergency Coordination, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA 5: Division of Viral Products, Office of Vaccines, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, Maryland, USA. andrew.lewis@fda.hhs.gov

Publication date: August 1, 2013

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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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