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Animal models are crucial to preclinical oncological research and drug development. Animal experiments must be performed in accordance with the 3R principles of replacement and reduction, if possible, and refinement where these procedures remain crucial. In addition, European Union legislations demand a continuous refinement approach, as well as pro- and retrospective severity assessment. In this study, an objective databased severity assessment was performed in murine models for pancreatic cancer induced by orthotopic, subcutaneous, or intravenous injection of Panc02 cells. Parameters such as body weight change, distress score, perianal temperature, mouse grimace scale, burrowing, nesting behavior, and the concentration of corticosterone in plasma and its metabolites in feces were monitored during tumor progression. The most important parameters were combined into a score and mapped against a reference data set by the Relative Severity Assessment procedure (RELSA) to obtain the maximum achieved severity for each animal (RELSAmax). This scoring revealed a significantly higher RELSAmax for the orthotopic model than for the subcutaneous and intravenous models. However, compared to animal models such as pancreatitis and bile duct ligation, the pancreatic cancer models are shown to be less severe. Data-based animal welfare assessment proved to be a valuable tool for comparing the severity of differently induced cancer models.
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; Brandstetter, Jakob 1 ; Talbot, Steven R 2
; Goldstein, Lea 1 ; Hoffmann, Lisa 1 ; Schildt, Anna 3 ; Joksch, Markus 4 ; Krause, Bernd 4 ; Jaster, Robert 5
; Palme, Rupert 6
; Zechner, Dietmar 1
; Vollmar, Brigitte 1 ; Kumstel, Simone 1
1 Rudolf-Zenker-Institute of Experimental Surgery, Rostock University Medical Center, 18057 Rostock, Germany;
2 Institute for Laboratory Animal Science, Preclinical Data Science, Hannover Medical School, 30625 Hannover, Germany;
3 Core Facility Multimodal Small Animal Imaging, Rostock University Medical Center, 18057 Rostock, Germany;
4 Department of Nuclear Medicine, Rostock University Medical Center, 18057 Rostock, Germany;
5 Division of Gastroenterology, Department of Medicine II, Rostock University Medical Center, 18057 Rostock, Germany;
6 Unit of Experimental Endocrinology, Department of Biological Sciences and Pathobiology, University of Veterinary Medicine, 1210 Vienna, Austria;