[Mutagen sensitivity of patients with laryngeal and oropharyngeal carcinoma].
BACKGROUND
Carcinogenesis in the larynx and oropharynx is often associated with excessive exposure to tobacco smoke and alcohol. However, attention is increasingly being focused on genetically determined mutagen sensitivities and on the mutagenic impact of xenobiotics. The purpose of this study was to evaluate the genotoxicity of phthalates (plasticizers widely used in synthetic materials), as well as nitrosamines and polycyclic aromatic carbohydrates, on laryngeal and oropharyngeal epithelia and peripheral lymphocytes of patients with laryngeal and oropharyngeal carcinomas.


METHODS
The comet assay was used to detect induced DNA strand breaks. Macroscopically healthy supraglottic and oropharyngeal epithelia of patients with laryngeal and oropharyngeal tumors, respectively, and lymphocytes were investigated with dibutyl phthalate (DBP), diisobutylphthalate (DiBP). N'nitrosodiethylamine (NDELA), and benzo[a]pyrene (BaP). The Olive Tail Moment (OTM) was used to quantify genotoxicity.


RESULTS
For the first time, the genotoxicity of DBP and DiBP was demonstrated in laryngeal and oropharyngeal epithelia, as well as in peripheral lymphocytes, of patients suffering from laryngeal and oropharyngeal carcinomas. OTM levels for NDELA were higher than for phthalates; levels for BaP were lower. Testing of lymphocytes and mucosa showed no significant differences among the various substances.


CONCLUSIONS
Phthalates show a genotoxic impact on epithelia of tumor patients. OTM levels were higher than in nasal and oropharyngeal mucosa of healthy donors in results reported earlier. Thus, specific susceptibilities to these xenobiotics need to be discussed. No such effect was demonstrated for NDELA and BaP. In tumor patients, no significant differences could be shown in mutagenic sensitivities in mucosal cells and lymphocytes.
Kleinsasser
N H
NH
Klinisch experimentelle Onkologie, Ludwig-Maximilians-Universität München. norbert.kleinsasser@hno.med.uni-muenchen.de
Harréus
U A
UA
Wallner
B C
BC
Kastenbauer
E R
ER
D000328:Adult; D000368:Aged; D001564:Benzo(a)pyrene / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D020552:Comet Assay; D004048:Diethylamines / Q000633:toxicity; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007822:Laryngeal Neoplasms / Q000209:etiology / Q000235:genetics*; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects; D009153:Mutagens; D009959:Oropharyngeal Neoplasms / Q000209:etiology / Q000235:genetics*; D010795:Phthalic Acids / Q000633:toxicity; D015262:Xenobiotics / Q000633:toxicity
D004048:Diethylamines; D009153:Mutagens; D010795:Phthalic Acids; D015262:Xenobiotics; D001564:Benzo(a)pyrene; C032279:phthalic acid