Altered genotoxicity in mucosal cells of head and neck cancer patients due to environmental pollutants.
The complexity of carcinogenesis in squamous cell cancer (SCC) of the upper aerodigestive tract requires examining environmental risk factors, including mutagen sensitivities to xenobiotics. Three environmental, occupational, and habitual pollutants - dibutylphthalate (DBP), diisobutylphthalate (DiBP), and N'nitrosodiethylamine (NDELA) - were submitted to genotoxicity testing on mucosal biopsy specimens of tumor and nontumor patients in vitro. The single-cell microgel electrophoresis (Comet) assay was applied to detect DNA strand breaks in human epithelial cells of the pharynx and larynx from nontumor patients, patients with SCC of the oropharynx and patients with SCC of the larynx. Genotoxicity was found for DBP, DiBP, and NDELA in cells derived from nontumor and tumor patients. With respect to phthalates, Olive tail moment (OTM) levels were higher in patients with SCC of the oropharynx and SCC of the larynx (P < 0.01), the latter showing even more pronounced genotoxicity for DiBP. Testing epithelial cells of the patients with either oropharyngeal or laryngeal SCC for NDELA demonstrated results similar to the nontumor patients. Present findings indicate heterogeneous mutagen sensitivities to some but not all xenobiotics.
Kleinsasser
N H
NH
Department of Otolaryngology, Head and Neck Surgery, Ludwig Maximilians University of Munich, Germany. norbert.kleinsasser@hno.med.uni-muenchen.de
Weissacher
H
H
Kastenbauer
E R
ER
Dirschedl
P
P
Wallner
B C
BC
Harréus
U A
UA
D000293:Adolescent; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000473:pathology*; D020552:Comet Assay; D003993:Dibutyl Phthalate / Q000009:adverse effects*; D004052:Diethylnitrosamine / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests; D009959:Oropharyngeal Neoplasms / Q000139:chemically induced / Q000473:pathology*; D015262:Xenobiotics / Q000009:adverse effects*
D015262:Xenobiotics; D003993:Dibutyl Phthalate; D004052:Diethylnitrosamine