MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

Multi-walled carbon nanotubes (MWCNTs) are extensively produced and used in composite materials and electronic applications, thus increasing risk of worker and consumer exposure. MWCNTs are an inhomogeneous group of nanomaterials that come in various lengths, shapes and with different metal contaminations, which makes hazard evaluation difficult. However, several studies suggest that length plays an important role in the toxicity induced by MWCNTs. How the length influences toxicity at the molecular level is yet to be characterized. Female C57BL/6 mice were exposed by single intratracheal instillation to 18, 54 or 162 µg/mouse of a short MWCNT (NRCWE-026, 847±102 nm in length) or long MWCNT (NM-401, 4048±366 nm in length). The two MWCNTs were extensively characterized. Lung tissues were harvested 24 h, 3 d and 28 d after exposure. We employed DNA microarrays, bronchoalveolar lavage fluid analysis, comet assay and dichlorodihydrofluorescein assay in order to profile the pulmonary responses. Bioinformatics tools were then applied to compare and contrast the expression profiles and to build a length dependent property-response matrix for gene-by-gene comparison. The toxicogenomic analysis of the global mRNA changes after exposure to the short, entangled NRCWE-026 or the longer, stiffer NM-401 showed high degree of similarities. The toxicity of both MWCNTs was driven by strong inflammatory and acute phase responses, which peaked at day 3 and was observed both in bronchoalveolar lavage cell influx and in gene expression profiles. The inflammatory response was sustained at post-exposure day 28. Also, at the sub-chronic level, we identified a sub-set of 14 fibrosis related genes that were uniquely differentially regulated after exposure to NM-401. Acellular ROS production occurred almost exclusively with NRCWE-026, however the longer NM-401 induced in vivo DNA strand breaks and differential regulation of genes involved in free radical scavenging more readily than NRCWE-026. Our results indicate that the global mRNA response after exposure to MWCNTs is length independent at the acute time points, but that fibrosis may be length dependent sub-chronic end point.JRC.H.6-Digital Earth and Reference Dat

Benign keratinizing cystic squamous cell tumour in the rat lung

Benign keratinizing cystic squamous cell tumours were induced in rat lungs by intratracheal instillation of 15 mg carbon black particles. In this species keratinizing cystic squamous cell tumours are frequently observed after inhalation of intratracheal instillation of particles. Microscopically, the tumours are formed by a sharply demarcated, mostly keratinized squamous epithelium. In the center of the mass there are usually large amounts of keratin and necrotic tumour tissue. Epithelium may be flattened to a thin layer of squamous cells, especially adjacent to pleura or interstitium surrounding major airways and vessels. Growth occurs mainly by peripheral extension into the alveolar spaces. Mitoses are rare. These benign tumours may progress to squamous cell carcinomas, which show destruction of the basement membrane, cellular atypia, disorientation of cells and frequent mitoses

Spontaneous neoplastic lesions in Harlan Sprague-Dawley rats

In a 24-months study, the spontaneous tumour spectrum of the Hsd:Sprague-Dawley stock was examined. Pituitary gland tumours were found in 20 per cent of the males and 39 per cent of the females. This relatively low incidence, compared to other SPRD stocks, had little effect on the survival of the females (50 per cent), due to the high incidence (76 per cent) of mammary gland tumours (predominantly fibroadenomas) resulted in unscheduled sacrifices of many female. Other common neoplasms in Hsd:Sprague-Dawley rats were benign medullary tumours (27 per cent in males, 11 per cent in females), C-cell adenomas (23 per cent in males, 28 per cent in females), and endometrial stromal polyps (22 per cent in females)

Spontaneous cystic keratinizing epithelioma in the lung of a Sprague-Dawley rat

A spontaneous cystic keratinizing epithelioma in the lung of a 704-days-old female Hsd:Sprague-Dawley rat is described. The rat has a white subpleural discoloration on 1 diaphragmatic lobe at necrospy. Microscopically, a central keratin mass, surrounded by a multilayered squamous epithelium of varying thickness, was found. In the periphery of the tumor, epithelial nests projected multifocally into the adjacent alveolar spaces. Immunohistochemical labeling of nuclei by PNAC (proliferating cell nuclear antigen) revealed proliferative activity in 1 or 2 peripheral cell layers in most locations. To the best of the authors' knowledge, this is the first report dealing with the morphological and immunohistochemical features of a spontaneous cystic keratinizing epithelioma in a rat

Morphometrische und funktionelle Untersuchungen an Nieren von Ratten der Staemme MWF/Ztm und LEW/Ztm waehrend der postnatalen Entwicklungs- und Reifungsphase; Gefoerdert durch die Deutsche Forschungsgemeinschaft -Sonderforschungsbereich 146: "Versuchstierforschung"

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Melanoma of the eye, mouse

Gross appearance. Microscopic features. Differential diagnosis. Comparison with other species

Calcification of the heart, hamster

Gross appearance. Microscopic features. Ultrastructure. Biological features. Comparison with other species