Genotoxicity of di-butyl-phthalate and di-iso-butyl-phthalate in human lymphocytes and mucosal cells.
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.
Kleinsasser
N H
NH
Department of Otolaryngology-Head and Neck Surgery, Ludwig-Maximilians-University Munich, Germany. norbert.kleinsasser@hno.med.uni-muenchen.de
Wallner
B C
BC
Kastenbauer
E R
ER
Weissacher
H
H
Harréus
U A
UA
D020552:Comet Assay / Q000706:statistics & numerical data; D004249:DNA Damage / Q000187:drug effects*; D003993:Dibutyl Phthalate / Q000031:analogs & derivatives / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009061:Mouth Mucosa / Q000187:drug effects*; D009153:Mutagens / Q000494:pharmacology; D009297:Nasal Mucosa / Q000187:drug effects; D009960:Oropharynx / Q000187:drug effects; D015262:Xenobiotics / Q000494:pharmacology
D009153:Mutagens; D015262:Xenobiotics; D008769:Methylnitronitrosoguanidine; D003993:Dibutyl Phthalate