Spontaneous Hibernomas in Sprague-Dawley Rats

• Published in: Toxicologic pathology Vol. 37; no. 4; pp. 547 - 552
• Main Authors: Bruner, Richard H., Novilla, Meliton N., Picut, Catherine A., Kirkpatrick, Jeannie B., O’Neill, Thomas P., Scully, Kathryn L., Lawrence, Wade B., Goodman, Dawn G., Saladino, Brett H., Peters, David G., Parker, George A.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-06-2009; Sage Publications
• Subjects: Adipose Tissue, Brown - pathology; Animals; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinogenicity Tests; Chemical agents; Female; Immunohistochemistry; Ion Channels - metabolism; Lipoma - epidemiology; Lipoma - pathology; Lipoma - veterinary; Male; Medical sciences; Mitochondrial Proteins - metabolism; Rats; Rats, Sprague-Dawley; Rodent Diseases - epidemiology; Rodent Diseases - pathology; Toxicology; Tumors; Uncoupling Protein 1; USA, North Carolina, Raleigh; USA, North Carolina; Sprague-Dawley rats; UCP-1; brown fat; hibernoma; brown adipose; carcinogenesis bioassay; Bioassay; Adipose tissue; Rat; Spontaneous; Rodentia; Carcinogenesis; Vertebrata; Mammalia; Hibernoma; Animal; Fat; Adipose tissue disorders; Benign neoplasm; Lipoma
• ISSN: 0192-6233; 1533-1601
• DOI: 10.1177/0192623309335061

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., β-adrenergic stimulation) that may target brown fat adipocytes.