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United States Department of Agriculture

Agricultural Research Service

Title: Morphological Effects of Pasteurella Multocida Type-D Dermonecrotoxin on Rat Osteosarcoma Cells in a Nude Mouse Model

Authors
item Dyer, N - ND STATE UNIV., FARGO, ND
item Haynes, J - IA STATE UNIV., AMES, IA
item Ackermann, Mark - IA STATE UNIV., AMES, IA
item Rimler, Richard

Submitted to: Journal of Comparative Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 23, 1998
Publication Date: N/A

Interpretive Summary: Toxin-producing bacteria, Pasteurella multocida, are the cause of severe progressive atrophic rhinitis of swine. Many of the clinical signs of this disease can be reproduced in pigs by inoculating them with the pure toxin alone. The toxin acts on rapidly growing bone cells causing atrophy of the nasal turbinates and twisting or shortening of the snout. The toxin has been shown to kill cells grown in tissue culture. This study was done to determine whether the toxin might have therapeutic value in preventing bone cell tumors in animals. Tumors were produced in immune deficient mice and the mice were treated with toxin. In contrast to expectations, the toxin seemed to enhance tumor growth and spread to other tissues. These findings suggest that Pasteurella multocida toxin has little or no therapeutic value for killing or preventing the spread of tumors of bone cell origin.

Technical Abstract: Of 15 athymic nude mice that received subcutaneous implants of a rat osteosarcoma cell line, two groups of four subsequently received either a short (group 1) or a more prolonged (group 2) course of subcutaneous injections of the dermonecrotic toxin (DNT) of Pasteurella multocida type D. The remaining seven mice (controls) received no DNT. Both groups of DNT-treated mice lost bodyweight as compared with controls. Tumour weight expressed as a percentage of body weight, increased in the four group 1 mice. Tumours in this group 1 were consistently larger than those in appropriate controls, indicating that this percentage was not simply a function of decreased body weight. The immunohistochemical labelling of proliferating cell nuclear antigen (PCNA) and morphometric analysis of intratumoral necrosis suggested that the DNT had a mitogenic effect and contributed to the neoplastic growth. The presence of foci of neoplastic osteoblasts in the lungs of some DNT-treated mice suggested that the enhanced tumour growth led to an increased incidence of metastasis.

Last Modified: 8/22/2014
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