Kleinsasser N H, Wallner B C, Kastenbauer E R, Weissacher H, Harréus U A
Department of Otolaryngology-Head and Neck Surgery, Ludwig-Maximilians-University Munich, Germany.
Teratog Carcinog Mutagen. 2001;21(3):189-96. doi: 10.1002/tcm.1007.
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.
邻苯二甲酸酯是广泛使用的增塑剂，先前一项使用彗星试验的研究已表明，邻苯二甲酸二丁酯（DBP）和邻苯二甲酸二异丁酯（DIBP）对上呼吸道和消化道人类黏膜细胞具有遗传毒性。此外，与非肿瘤患者相比，喉或口咽鳞状细胞癌患者表现出更高的遗传毒性敏感性。其他作者已证明另一种邻苯二甲酸酯会对人类淋巴细胞造成DNA损伤。本研究的目的是确定在上呼吸道和消化道黏膜细胞或淋巴细胞中，对DBP及其异构体DIBP的遗传毒性敏感性之间是否存在相关性。采用单细胞微凝胶电泳试验（彗星试验）检测上呼吸道和消化道人类上皮细胞中的DNA链断裂（n = 132个样本）。从非肿瘤患者和口咽鳞状细胞癌患者的口咽部采集人类黏膜。同时采集喉鳞状细胞癌患者的喉黏膜。从外周血中分离出外周淋巴细胞（n = 49个样本）。所研究的外源化学物分别为DBP、DIBP以及作为阳性对照的N-甲基-N'-硝基-N-亚硝基胍（MNNG）。进行统计分析时，采用了Pearson的SPSS相关分析和Wilcoxon检验。发现DBP和DIBP对上皮细胞和淋巴细胞具有遗传毒性（P < 0.001）。MNNG造成了严重的DNA损伤。在分析DBP和DIBP的结果时，黏膜细胞中的遗传毒性影响呈现中度相关性（r = 0.570）。淋巴细胞中的相关性相同（r = 0.570）。由于多种原因，包括可能的外源性雌激素影响、过氧化物酶体增殖和膜不稳定等，邻苯二甲酸酯已被作为一种潜在的健康危害进行研究。本研究表明，DBP和DIBP分别对人类黏膜细胞和淋巴细胞具有相关的DNA损伤作用。
