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

Abstract

SummaryCystic 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/m3) to 10.7 % (7.5 mg/m3). 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 in more than three peripheral cell layers of cystic keratinizing squamous cell carcinomas and keratinizing squamous cell carcinomas. The wall of keratinizing cysts showed no or a weak reaction.