Pulmonary cystic keratinizing squamous cell lesions of rats after inhalation/instillation of different particles

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 1997-12, Vol.49 (6), p.433-446
• Main Authors: Rittinghausen, S., Mohr, U., Dungworth, D.L.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Aerosol, inhalation; Aerosols; Air Pollutants - toxicity; Animals; B( a)P; Benz(a)Anthracenes - toxicity; benzo( a)pyrene; Benzo(a)pyrene - toxicity; Biological and medical sciences; Carbon black; Carcinogenesis, carcinogens and anticarcinogens; Carcinoma, Squamous Cell - chemically induced; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, squamous cell, keratinizing, lung; Cell Division - drug effects; Coal; Coal oven exhaust; Coal Tar - toxicity; Crocidolite instillation; DB ( ah) A; dibenz( ah)antracene; Diesel exhaust particles; Epithelioma, cystic, keratinizing, lung; Female; Gas, irritant; Immunohistochemistry; Inhalation, different particles; Instillation, different particles; Intubation, Intratracheal; Irritant gas; Keratinizing cysts, lung; Keratinizing squamous cell lesion, pulmonary; Lung - drug effects; Lung Neoplasms - chemically induced; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung, inhalation, different particles; Lung, keratinizing squamous cell lesion; Medical sciences; Particle Size; Particles, inhalation; Particles, instillation; Physical agents; Proliferating Cell Nuclear Antigen - metabolism; Proliferative cell nuclear antigen (PCNA); Pulmonary keratinizing squamous cell lesion; Rats; Rats, Wistar; Squamous metaplasia, lun; Tar/pitch condensation aerosol; Titanium dioxide; Tumors; Vehicle Emissions - toxicity
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/S0940-2993(97)80131-5

Cystic keratinizing squamous cell lesions from three inhalation studies (Study A, B, C) and one intratracheal instillation study (Study D) in rats were reclassified and a certain number of lesions examined immunohistochemically for PCNA (proliferating cell nuclear antigen) as a marker of cellular proliferation. The following classification was used: squamous cell metaplasia with marked keratinization, keratinizing cyst, cystic keratinizing epithelioma, cystic keratinizing squamous cell carcinoma, keratinizing squamous cell carcinoma and non-keratinizing squamous cell carcinoma. In study A (inhalation of coal oven exhaust and subcutaneous injection of a high dose of DB ( ah)A) 49.3 % of rats developed cystic keratinizing squamous cell carcinomas. Inhalation of coal oven exhaust gas together with intratracheal instillation of crocidolite or subcutaneous injection of a low dose DB( ah)A (dibenz( ah)anthracene) resulted in cystic keratinizing squamous cell carcinomas in 23 % to 24 % of the rats. High incidences of cystic squamous cell carcinomas in the range of 31.9 % to 76.4 % were observed in rats of Study B1 after a 10-months exposure to tar/pitch condensation aerosol (different B( a)P (benzo( a)pyrene) concentrations) with added carbon black in some groups. After a 20-months exposure period to the same inhalation atmospheres (Study B2) the incidence of squamous cell carcinomas was increased up to 95.8 %. Exposure of rats to various concentrations of unfiltered diesel exhaust (Study C) resulted in incidences of cystic keratinizing epitheliomas ranging from 2.5 % (2.5 mg/m 3) to 10.7 % (7.5 mg/m 3). Epitheliomas were also observed in 16.2 % of carbon black and 16.0 % of titanium dioxide exposed rats. Only a few cystic keratinizing squamous cell carcinomas occurred. In the intratrachel instillation study (Study D) increased incidences of cystic keratinizing epitheliomas occurred in rats exposed to native diesel exhaust particles (16.7 %), high dose of extracted diesel exhaust particles (14.6 %), extracted printex 90-carbon black particles (18.8 %), and extracted printex 90-carbon black particles + B( a)P (18.8 %). High indicences of cystic keratinizing squamous cell carcinomas were noted in rats that received 15 mg B( a)P (14.6 %) or 30 mg B( a)P (72.7 %) intratracheally. Immunohistochemical labeling of nuclei with PCNA demonstrated proliferative activity in one or two (and focally more than two) peripheral cell layers of cystic keratinizing epitheliomas and