Introduction:
Nasal epithelium represents an effective barrier against inhalative substances. For
chronic rhinosinusitis (crs) previous studies demonstrated the existence of hypoxic
mucosal areas endonasally. A significant damage of the epithelium caused by the ubiquitously
present environmental pollutant NO2 was verified by our group. Objective of this study
was to investigate the impact of hypoxia on genotoxicity and the extent of cell damage
of nasal epithelium pre-damaged by NO2.
Methods:
Nasal mucosa was obtained from 12 patients with crs. Therefrom isolated primary mucosa
cells were cultivated under air-liquid interface conditions. The NO2 exposition was
carried out with the subtoxic concentration of 0.1ppm for 1 hour. Subsequently cultivation
took place either under normoxic or hypoxic conditions (under 1% O2). The transepithelial
resistance as well as the paracellular permeabilty were determined. For the analysis
of genotoxicity the comet assay was used.
Results:
Under hypoxic conditions there was a significantly stronger reduction of the transepithelial
resistance as well as a higher FD4 passage. Furthermore, the measures showed an increased
genotoxicity after exposition to NO2 followed by hypoxic cultivation.
Discussion:
We could demonstrate a significantly higher damage of the epithelial integrity caused
by NO2 with a subsequent hypoxia in vitro. NO2 leads already in non-genotoxic and
non-cytotoxic concentration under hypoxia to a damage of the epithelial barrier. Following
a damage of the epithelium by NO2 there is an increased genotoxicity under hypoxia.
Epithelial repair mechanisms appear to get reduced. A higher vulnerability by NO2
among patients with crs has to be postulated.
