Formaldehyde is cytotoxic and carcinogenic to the rat nasal respiratory epithelium inducing
tumors after 12 months.
Glutaraldehyde is also cytotoxic but is not carcinogenic to nasal epithelium even after 24 months. Both
aldehydes induce similar acute and subchronic histopathology that is characterized by
inflammation,
hyperplasia, and squamous
metaplasia. Because early
aldehyde-induced lesions are microscopically similar, we investigated whether transcriptional patterns using
cDNA technology could explain the different
cancer outcomes. Treatments included 1-, 5-, or 28-day exposure by nasal instillation of
formaldehyde solution (400 mM) or
glutaraldehyde solution (20 mM). Animals were euthanized and the nasal respiratory epithelium removed for gene expression analysis and a subset of rats treated for 28 days was processed for microscopic examination.
RNA was isolated and processed for expression assessment using Clontech Atlas Toxicology II Arrays. Both
aldehydes induced
hyperplasia, squamous
metaplasia, and inflammatory infiltrates with scattered apoptotic bodies in the epithelium covering
luminal surfaces of the nasoturbinate, maxilloturbinate, and nasal septum. A subset of 80 genes that were the most variant between the treated and control included the functional categories of DNA repair and apoptosis. Hierarchical clustering discriminated chemical treatment effects after 5 days of exposure, with 6 clusters of genes distinguishing
formaldehyde from
glutaraldehyde. These data suggest that although both
aldehydes induced similar short-term cellular phenotypes, gene expression could distinguish
glutaraldehyde from
formaldehyde. The gene expression patterns suggest that
glutaraldehyde's lack of carcinogenicity may be due to its greater toxicity from lack of DNA-repair, greater mitochondrial damage, and increased apoptosis.