Resistance of Copenhagen rats to chemical induction of glutathione S- transferase 7-7-positive liver foci

Copenhagen (Cop) rats are completely resistant to the chemical induction of mammary adenocarcinomas, but their susceptibility to hepatocarcinogenesis is virtually unknown. Rat liver is a well- characterized and easily manipulated tissue in which to study carcinogenesis. Therefore, if Cop rats are resistant to hepatocarcinogenesis, studies into resistance mechanisms may be feasible. Male Cop and F344 rats, 7-8 weeks old, were initiated using either N-nitrosodiethylamine (DEN) (200 mg/kg, i.p.) or a two-thirds partial hepatectomy (PH) followed by N-methyl-N-nitrosourea (MNU) (60 mg/kg, i.p.). The rats were then promoted using a modified resistant hepatocyte (RH) protocol (a combination of four doses of 2- acetylaminofluorene (2-AAF) and a single dose of CCl4 that provides a selective mitotic stimulus for initiated cells). Six weeks after initiation the rats were killed and liver sections were stained for glutathione S-transferase 7-7 (GST 7-7), a marker for putative preneoplastic hepatocytes. Cop rats were found to be highly resistant, having a approximately 9- and approximately 27-fold smaller percentage of liver area occupied by GST 7-7-positive foci than susceptible F344 rats following initiation by DEN and MNU respectively. Furthermore, gross liver nodules did not form in any of the Cop rats, whereas all F344 rat livers contained nodules. Hepatic necrosis caused by DEN during initiation, and CCl4 during promotion is necessary to stimulate compensatory hepatocyte division. We demonstrated that these agents do indeed increase serum transaminase levels and produce histologic evidence of necrosis in Cop rats. In order for liver foci to grow rapidly in the RH protocol, the surrounding normal hepatocytes must be mito-inhibited by 2-AAF. We found that the degree of mito-inhibition of normal hepatocytes by 2-AAF is the same in Cop and F344 rats. These results show that the Cop rat is highly resistant to the chemical induction of putative preneoplastic liver foci and nodules.      

Desmoplastic fibroma of the proximal ulna

A young man presented with desmoplastic fibroma in the proximal ulna. This rare tumour was treated by curettage and bone grafting.     

Effects of immunosuppression on the development of cochlear disease in the MRL-Fas(lpr) mouse

OBJECTIVES: The MRL-Fas(lpr) mouse, an animal that spontaneously develops multisystemic autoimmune disease, has been proposed as model of immune-mediated inner ear disease. Previous studies revealed that this mouse manifested elevated auditory brainstem response thresholds, hydropic degeneration of strial cells, and antibody deposition within strial capillaries. As the etiology of the observed strial disease may be immune, genetic, or uremic, a study was designed to attempt to delineate between these possible etiologic factors. STUDY DESIGN: Prospective, controlled animal study. METHODS: Dexamethasone, which is known to suppress autoantibody production and glomerulonephritis in these animals, was administered systemically on a daily basis to experimental animals, beginning at 6 weeks of age. Control animals received no treatment. Animals were allowed to age, with control animals predictably manifesting systemic disease at 20 weeks of age, at which point all animals were sacrificed. RESULTS: Animals receiving dexamethasone treatment manifested a significant reduction in serum immunoglobulin levels, lymphoid hyperplasia, and a significant improvement in the level of renal function. However, morphologic analysis revealed a persistence of strial disease despite the elimination of strial antibody deposition. CONCLUSION: The results of this experiment support the hypothesis that genetic mechanisms may be responsible for the observed strial disease. Further studies are under way to confirm these findings.     

Cytokinetic and morphological changes in the lungs and lung-associated lymph nodes of rats after inhalation of fly ash

Fischer-344 rats (male and female) were exposed to 36 mg/m³ of fluidized bed coal combustion fly ash or sham-exposed for 7 hr/day, 5 days/week for 4 weeks, and sacrificed after 2 or 4 weeks of exposure and at 2, 22, and 42 weeks after the end of exposure. Animals were injected with tritiated thymidine 2 hr before sacrifice and autoradiographs prepared from 1-μm sections of lung and lymph node tissue embedded in glycol methacrylate plastic. Differences in labeling indices of pulmonary epithelial cells, alveolar macrophages, airway epithelial cells, and cells of the lung-associated lymph nodes between the exposed and control animals were maximal after 2 and 4 weeks of exposure. Labeling indices for lung epithelial cells were about the same in control and exposed animals at 2, 22, and 42 weeks after the end of exposure. However, these values were elevated relative to earlier control levels. In contrast, morphological changes in the fly ash-exposed animals were most prominent after the end of the exposure. These changes included thickening of the alveolar walls, clusters of particle-filled macrophages in the alveolar region, and perivascular inflammation. Additionally, there were small granulomas in the alveolar region at 42 weeks after the end of exposure. Granulomas were also formed in the lung-associated lymph nodes and bronchus-associated lymphoid tissue. We conclude that the inhalation of fly ash alone had little detrimental effect upon the rat lung. However, the increases in proliferation indicate the potential for fly ash combined with a carcinogen to enhance the carcinogen's effect.