Altered genotoxicity in mucosal cells of head and neck cancer patients due to environmental pollutants

Abstract

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.

The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay.

“…Using the alkaline comet assay, researchers have found evidence of genotoxicity with in vitro studies examining lymphocytes and mucosal cells of the upper aerodigestive tract after exposure to DBP and DiBP (Kleinsasser et al 2000a(Kleinsasser et al , 2000b(Kleinsasser et al , 2001. In another study using the alkaline comet assay on human leukocytes, an association between MEHP and DEHP and increased tail moments was found (Anderson et al 1999).…”

“…Recent in vitro studies using the alkaline comet assay (single-cell gel electrophoresis) found di-n-butyl phthalate (DBP) and di-isobutyl phthalate (DiBP) to be genotoxic in human epithelial cells of the upper aerodigestive tract (Kleinsasser et al 2000a), as well as in mucosal cells and lymphocytes (Kleinsasser et al 2000b). Additionally, the comet assay was used to detect DNA damage in human lymphocytes induced by in vitro exposure to DEHP and MEHP (Anderson et al 1999).…”

Potential use of the comet assay in the clinical management of cancer

“…Environmental mutagens caused increased DNA damage and genotoxicity in cancer group compared to controls (12) Head and Neck Fine-needle aspirates taken 1, 2 or 3 min after local field radiotherapy to the index (largest) lymph node…”

Stellenwert der Einzelzell Mikrogelelektrophorese in der Ökogenotoxikologie

“…Auch die DNA-Schädigung durch Insektizide wie Pentachlorphenol und Lindan [22] sowie Genotoxizitäts-und Zytotoxizitätsstudien an Olaflur wurden an oropharyngealer Schleimhaut und an Lymphozyten mit dem Comet Assay durchgeführt [23]. Aufgrund der unterschiedlichen Ergebnisse von einzelnen Spendern in den ersten Untersuchungen an humaner Schleimhaut [9,20] [25,26]. Auch andere Messungen an laryngealer Schleimhaut von Larynxkarzinompatienten ergaben erhöhte Schädigungsraten verglichen mit Spendern ohne Malignom [27].…”