Pathological Changes Induced by Formaldehyde in Open-Ended Rat Tracheal Implants Preexposed to Benzo(a)pyrene

Abstract

The promotion effects of 0.1% formaldehyde (HCHO) in phosphate-buffered saline (PBS) were tested in rat tracheal implants preexposed to a minimal carcinogenic dose of 468 μg benzo(a)pyrene (BAP) released over one month from 865 μg BAP-beeswax pellets. At the time of pellet removal, the tracheas were made into open-ended, flow-through, tracheal implants (FTTI), and exposed twice/week to HCHO for 30 weeks. Morphological alterations in the FTTI were monitored biweekly by collection of exfoliated cells from the luminal washings for cytopathologic diagnosis, and periodically by sacrificing animals for histopathology. FTTI exposed to the BAP followed by6 30 weeks of HCHO had extensive squamous metaplasia, a high proliferation index of 7.87 [3H]thymidine-labeled cells/mm basement membrane, and foci of moderate and marked atypia. Clear diagnosis of some of the lesions was difficult because of the acute toxic effects of the repeated exposures to HCHO. These effects were seen in the tissues as well as in the exfoliated cells, which attest to the latter as an efficient, non-destructive, method for determining the responses of the tracheas to exposure to toxic and carcinogenic agents. FTTI exposed to BAP followed by twice weekly PBS, had a mostly flattened epithelium, and a low proliferation index (0.39). FTTI exposed to beeswax pellets, followed by the HCHO had a relatively high proliferation index (4.20) in a mucociliary epithelium exhibiting some basal cell hyperplasia. Control FTTI had a normal mucociliary epithelium with a proliferation index of 1.52 [3H]thymidine labeled cells/mm basement membrane.