Upper Respiratory Tract Tumors in Cpb:WU (Wistar Random) Rats

Abstract

A survey is given of upper respiratory tract tumors in Cpb:WU (Wistar random) rats. Data were collected from ten 24-to 30-month toxicity/carcinogenicity studies and from one 12-month study. Nasal tumors may lead to dyspnea, mouth breathing, and nasal discharge. These clinical signs mainly occurred in rats bearing squamous cell carcinomas. The large nasal tumors were often osteolytic, they invaded the subcutis over the premaxilla, resulting in swellings on the back of the nose, and extended into the brain. The incidence of nasal tumors in untreated male controls was 1.1% (7/661), the tumors invariably being squamous cell carcinomas. There were no nasal tumors found in untreated female controls. The type of compound-induced nasal tumor most frequently observed was adenocarcinoma (of the olfactory epithelium) followed, in order of decreasing incidence, by squamous cell carcinoma, carcinoma in situ, polypoid adenoma, Schwannoma, and carcinosarcoma. It was proposed that adenocarcinomas of the olfactory epithelium should be classified as neuroepitheliomas. It was also suggested that squamous cell carcinomas, seen in association with necrotizing inflammation of an incisor tooth, should be considered as part ofthe malocclusion syndrome. No spontaneous tracheal tumors were observed, and only one out of 422 untreated female controls (0.2 %) was seen to have a laryngeal tumor, an adenoma. Induced laryngeal tumors included carcinoma in situ, squamous cell carcinoma, and adenocarcinoma. Squamous cell carcinoma was the only type of treatment-related tracheal tumor found. The incidences of induced laryngeal and tracheal tumors were very low, and in no case were these tumors statistically significantly different from the respective incidences in controls.

Spontaneous Neoplasms in Control Wistar Rats: A Comparison of Reviews

“…Musculoskeletal and respiratory systems of Wistar rats are rarely affected by spontaneous neoplasms (Bomhard et al, 1986;Kroes et al, 1981;Feron et al, 1990;Novilla et al, 1991). In this review, 0.6% of all neoplasms were in these tissues, an incidence lower than the 1.9% of our previous review but comparable to the 0.5% reported in BOR:WISW rats.…”

The receptor NLRP3 is a transcriptional regulator of TH2 differentiation

“…In addition, we also observed ten independent clusters of genes encoding products related to the cell cycle, regulation of transcription, RNA processing, protein interactions, metabolic processes, programmed cell death, the endoplasmic reticulum-nucleus signaling pathway, epigenetic modification, cytoskeleton modification and import into the nucleus (data not shown). In the third group (3,252 genes with similar expression in Nlrp3 −/− and wild-type T H 2 cells), we observed only two clusters of genes encoding products related to DNA repair and microtubule-based transport (Supplementary Fig. 4b).…”

“…However, reports suggest that NLRP3 protein is expressed not only in myeloid cells but also in epithelial cells 2,3 or lymphoid cells 4 . Classic activators of NLRP3 have been shown to induce the production of IL-1β by various epithelial cells, such as retinal epithelial cells 2 , or renal tubular cells 3 . In the context of lymphoid cells, expression of NLRP3 has been detected in both mouse CD4 + T cells and human CD4 + T cells 4 .…”

Upper Respiratory Tract Lesions in Inhalation Toxicology

“…Homburger (1975) reported induction of laryngeal carcinomas in Syrian hamsters exposed to cigarette smoke for up to 24 months. Feron et al (1982Feron et al ( , 1990 reported the induction of a small number of laryngeal carcinomas in rats and hamsters inhaling acetaldehyde or propylene oxide for 24 months. Conversely, there are numerous published reports of chronic inhalation exposures of rodents to irritant compounds such as tobacco smoke (Dalbey et al, 1980), ozone (Boorman et al, 1994), hexachlorocyclopentadiene (National Toxicology Program [NTP], 1994), and molybdenum trioxide (NTP, 1997) in which laryngeal squamous metaplasia was induced but progression to neoplasia was not present, even after lifetime exposure.…”