title: Comparing the genotoxic sensitivities of human peripheral blood lymphocytes and mucosa cells of the upper aerodigestive tract using the Comet assay.
abstract: Carcinogenesis in the upper aerodigestive tract is influenced by multiple factors. Besides tobacco and alcohol consumption, specific pollutants such as phthalates, nitrosamines, and polycyclic aromatic carbohydrates may be important in tumor initiation. Genetic factors related to mutagen sensitivity and DNA repair capacity also play a role. The aim of this study was to investigate whether human peripheral blood lymphocytes and mucosal epithelium of the upper aerodigestive tract, the target for volatile and liquid xenobiotics, are equally sensitive to genotoxic agents. The Comet assay was used to detect for DNA damage induced by genotoxic agents in mucosal epithelial cells and peripheral blood lymphocytes of 60 volunteers. Mucosa was harvested from larynx, oropharynx, and inferior nasal turbinates. Xenobiotics investigated were dibutylphthalate (DBP), diisobutylphthalate (DiBP), N'-nitrosodiethylamine (NDELA), benzo[a]pyrene (B[a]P), and N'-methyl-N'-nitro-N-nitrosoguanidine (MNNG). DBP, DiBP, B[a]P, NDELA and MNNG induced a significant increase in DNA migration in both cell populations. Peripheral blood lymphocytes were more sensitive than mucosal cells to DBP and DiBP, but not to NDELA and B[a]P. The correlation, in terms of DNA migration, between lymphocytes and mucosal cells among volunteers was relatively poor. Based on the poor correlation in response between the two cell types, the sensitivity of peripheral blood lymphocytes to genotoxic agents appears to be a poor predictor of sensitivity in the target cells of the upper aerodigestive tract. Further attention should be focused on intra-individual mutagen sensitivities and inter-individual genetic differences as regards susceptibility to upper aerodigestive tract cancer.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Klinisch Experimentelle Onkologie, Ludwig-Maximilians-University Munich, Pettenkoferstr. 4a, D-80336, Munich, Germany. norbert.kleinsasser@hno.med.uni-muenchen.de
authors.forename: N H
authors.initials: NH
authors.lastname: Kleinsasser
authors.forename: B C
authors.initials: BC
authors.lastname: Wallner
authors.forename: E R
authors.initials: ER
authors.lastname: Kastenbauer
authors.forename: R K
authors.initials: RK
authors.lastname: Muenzenrieder
authors.forename: U A
authors.initials: UA
authors.lastname: Harréus
mesh_terms: D000328:Adult; D000428:Alcohol Drinking; D001564:Benzo(a)pyrene / Q000494:pharmacology; D020552:Comet Assay / Q000706:statistics & numerical data; D004249:DNA Damage; D004052:Diethylnitrosamine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D008875:Middle Aged; D009153:Mutagens / Q000494:pharmacology*; D009297:Nasal Mucosa / Q000187:drug effects; D009960:Oropharynx / Q000187:drug effects*; D010795:Phthalic Acids / Q000494:pharmacology; D012907:Smoking; D015262:Xenobiotics / Q000494:pharmacology
chemical_list: D009153:Mutagens; D010795:Phthalic Acids; D015262:Xenobiotics; D008769:Methylnitronitrosoguanidine; D001564:Benzo(a)pyrene; D004052:Diethylnitrosamine