Spontaneous Hibernomas in Sprague-Dawley Rats

Biotechnics, LLC, Hillsborough, North Carolina 27278, USA.
Toxicologic Pathology (Impact Factor: 2.14). 05/2009; 37(4):547-52. DOI: 10.1177/0192623309335061
Source: PubMed


Hibernomas are rare neoplasms originating in brown adipose tissue of humans and other animal species, including laboratory animals. Background incidence values for these tumors in all common strains of laboratory rats are generally accepted as being <0.1%. Between April 2000 and April 2007, however, sixty-two hibernomas (an overall prevalence of 3.52%) were observed in a total of 1760 Sprague-Dawley rats assigned to three carcinogenesis bioassays at two separate research laboratories. All rats were obtained from Charles River's breeding facilities in either Portage, Michigan, or Raleigh, North Carolina. Tumors (twenty-nine benign and thirty-three malignant) were randomly distributed among test article-treated and control groups and were considered to be spontaneous. Most tumors originated in the thoracic cavity, and they were usually described as soft, mottled to tan masses with nodular to lobulated profiles. Immunohistochemical procedures for uncoupling protein 1 (UCP1) confirmed brown adipose tissue as the site of origin rather than white fat. The marked increase in hibernomas in our studies suggests that greater numbers of spontaneous hibernomas may be sporadically encountered in future carcinogenesis studies with Sprague-Dawley rats. The increased potential for hibernomas to arise as spontaneous neoplasms has important implications in studies involving peroxisome proliferators-activated receptor (PPAR) drugs, lipophilic environmental chemicals (e.g., polychlorinated biphenyls), and other molecules or physiologic processes (e.g., beta-adrenergic stimulation) that may target brown fat adipocytes.

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Available from: Brett Saladino, Mar 28, 2014
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    • "They are rare tumors in all species including humans but they appear to be more commonly reported in rats (22Coleman 1980; 1Al Zubaidy and Finn 1983; 104Stefanski et al. 1987; 23Coleman 1989; 14Bruner et al. 2009). A recent report has shown an increase in incidence in a colony of Sprague-Dawley rats (14Bruner et al. 2009). These tumors can be stained immunocytochemically using antisera to mitochondrial uncoupling protein (UCP-1), a protein essential for the thermogenic properties of brown fat in mammals (14Bruner et al. 2009). "
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    ABSTRACT: Hibernomas are uncommon benign tumors of brown fat that occur in humans and various animal species. They have not been observed in the orbit of dogs, humans, or other animals. Here we report clinical, light and electron microscopic, and immunohistochemical features of a series of 7 hibernomas arising in the orbital region of dogs. These neoplasms occurred in adult dogs with no breed predilection. The mean age of the affected dogs was 10.4 years (range, 8-13 years). All neoplasms presented as soft lobular masses composed of predominantly round or polygonal neoplastic cells with granular eosinophilic and vacuolated cytoplasm resembling adipocytes. The cytoplasm contained large numbers of pleomorphic mitochondria with dense matrices and indistinct cristae. Immunohistochemical evaluation confirmed positive labeling of neoplastic cells from all cases with uncoupling protein 1 (UCP-1) consistent with brown fat differentiation. Interestingly, rare neoplastic cells also expressed myogenin and myoD, possibly suggesting a common progenitor cell for neoplastic brown adipose and skeletal muscle cells.
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