Kleinsasser N H, Weissacher H, Kastenbauer E R, Dirschedl P, Wallner B C, Harréus U A
Department of Otolaryngology, Head and Neck Surgery, Ludwig Maximilians University of Munich, Germany.
Eur Arch Otorhinolaryngol. 2000;257(6):337-42. doi: 10.1007/s004059900220.
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.
上呼吸消化道鳞状细胞癌(SCC)致癌作用的复杂性需要对环境危险因素进行研究,包括对外源生物的诱变敏感性。三种环境、职业和习惯性污染物——邻苯二甲酸二丁酯(DBP)、邻苯二甲酸二异丁酯(DiBP)和N-亚硝基二乙胺(NDELA)——在体外对肿瘤患者和非肿瘤患者的黏膜活检标本进行了遗传毒性测试。单细胞微凝胶电泳(彗星)试验用于检测非肿瘤患者、口咽SCC患者和喉SCC患者的咽和喉人类上皮细胞中的DNA链断裂。在非肿瘤患者和肿瘤患者来源的细胞中发现了DBP、DiBP和NDELA的遗传毒性。对于邻苯二甲酸盐,口咽SCC患者和喉SCC患者的橄榄尾矩(OTM)水平较高(P < 0.01),后者对DiBP的遗传毒性更为明显。对患有口咽或喉SCC的患者的上皮细胞进行NDELA检测,结果与非肿瘤患者相似。目前的研究结果表明,对某些但并非所有外源生物存在异质诱变敏感性。