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Beside the cytotoxic effect of fluorides, also a minor genotoxic impact on human mucosa and on peripheral lymphocytes could be demonstrated using the Comet assay. Further investigations are warranted to examine fluorides in a model allowing for repeated or long term incubations on structurally intact human mucosa in vitro. Such a model will help to distinguish between DNA damage that may be repaired successfully and other impairments that may show an additive character in repetitive or chronic exposure in vivo.

The genotoxicity of phthalates, widely used plasticizers, has been shown previously for di-butyl-phthalate (DBP) and di-iso-butyl-phthalate (DBP) in human mucosal cells of the upper aerodigestive tract in a previous study using the Comet assay. Furthermore, higher genotoxic sensitivities of patients with squamous cell carcinomas of either the larynx or the oropharynx compared to non-tumor patients were described. Other authors have demonstrated DNA damage by a different phthalate in human lymphocytes. It was the aim of the present study to determine whether there is a correlation between the genotoxic sensitivities to DBP and its isomer DiBP in either mucosal cells or lymphocytes. The single-cell microgel electrophoresis assay (Comet assay) was applied to detect DNA strand breaks in human epithelial cells of the upper aerodigestive tract (n=132 specimens). Human mucosa was harvested from the oropharynx in non-tumor patients and patients with squamous cell carcinomas of the oropharynx. Laryngeal mucosa of patients with laryngeal squamous cell carcinomas was harvested as well. Peripheral lymphocytes (n=49 specimens) were separated from peripheral blood. Xenobiotics investigated were DBP, DiBP, and N'methyl-N'-nitro-N-nitrosoguanidine (MNNG) as positive control, respectively. For statistical analysis, the SPSS correlation analysis according to Pearson and the Wilcoxon test were performed. Genotoxicity was found for DBP and DiBP in epithelial cells and lymphocytes (P<0.001). MNNG caused severe DNA damage. In analyzing DBP and DiBP results, genotoxic impacts in mucosal cells showed an intermediate correlation (r=0.570). Correlation in lymphocytes was the same (r=0.570). Phthalates have been investigated as a potential health hazard for a variety of reasons, including possible xenoestrogenic impact, peroxisome proliferation, and membrane destabilization. The present investigation suggests a correlated DNA-damaging impact of DBP and DiBP in human mucosal cells and in lymphocytes, respectively.

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In addition to tobacco and alcohol consumption, pollutants found in certain industries and in the environment play an important role in carcinogenesis in the upper aerodigestive tract. The aim of the present study was to investigate whether vanadium pentoxide may have a genotoxic effect on human mucosal cells and lymphocytes. The single cell microgel electrophoresis assay (Comet assay) was used to detect DNA damage induced by vanadium pentoxide in human nasal epithelia (n = 11) and in lymphocytes (n = 11). Mucosa was harvested from inferior nasal turbinates, while lymphocytes were obtained via venous puncture. Vanadium pentoxide was applied at concentrations of 0.06 mM, 0.12 mM, 0.24 mM, and 0.47 mM. Aqua bidestillata served as solvent and negative control and N-methyl-N'-nitro-N-nitrosoguanidine at 0.07 mM (MNNG) was used as positive control. The trypan blue exclusion test was applied to assess cytotoxicity. Whereas vanadium pentoxide induced dose-dependent DNA migration in lymphocytes, mucosal cells did not show comparable genotoxic effects. Cytotoxic effects allowed for viabilities exceeding 80%. The results indicate that vanadium pentoxide is capable of inducing single-strand-breaks and/or alkali-labile damage in the DNA of human lymphocytes. By contrast, mucosal cells proved not to be sensitive in this setting. Thus, a possible role of vanadium in the tumorigenesis of head and neck cancer appears unrelated to direct genotoxic effects.

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