Genotoxic effects in human epithelial cells of the upper aerodigestive tract.

Background: In numerous epidemiologic studies, environmental and occupation al substances such as sodium dichromate (Na2Cr2O7), benzo[a]pyren (B(a)P), and N'nitroso-diethanolamine (NDELA) have been shown to be of potential car cinogenic risk on human epithelial cells in the upper aerodigestive tract. Methods: Using the alkaline microgel electrophoresis technique (comet assay ), mucosal cells isolated from biopsies of the upper aerodigestive tract (n ose, paranasal sinuses, mouth, pharynx, larynx, and tonsils) were used to a nalyze target sites for different genotoxic substances and specific sensiti vities of each donor. The cells were freshly isolated by enzymic digestion. 0.5 - 1 x 10(6) cells per donor were obtained with viabilities between 80 - 100 %. After in vitro incubation, the cells were subsequently subjected t o the single cell microgel electrophoresis assay. Results were evaluated re garding the personal history of each donor, focusing on previous exposure t o tobacco, alcohol, and occupational compounds. Results: Na2Cr2O7 induced s trong genotoxic damage in the nasal and paranasal sinus epithelia as well a s in mucosa cells of the larynx. NDELA caused significant damage in mouth c avity epithelia and showed also to be harmful towards mucosa of pharynx and larynx. B(a)P induced fewer DNA strand breaks in mucosal cells of mouth, p harynx and larynx. Significant differences between individuals were apparen t for tissue samples from different donors. The genotoxic damage induced in cells of donors with a history of chronic alcohol consumption was signific antly higher than in cells of patients without chronic abuse of alcohol. Co nclusions: The data shows that DNA damage in human epithelial cells of the upper aerodigestive tract induced by environmental and occupational substan ces can be demonstrated using the microgel electrophoresis technique. The i nfluence of chronic alcohol consumption on the genotoxic effects of substan ces such as NDELA and B(a)P showed the importance of evaluating preexisting compounding factors.