Kleinsasser N H, Wallner B C, Kastenbauer E R, Muenzenrieder R K, Harréus U A
Department of Otolaryngology - Head and Neck Surgery, Klinisch Experimentelle Onkologie, Ludwig-Maximilians-University Munich, Pettenkoferstr. 4a, D-80336, Munich, Germany.
Mutat Res. 2000 Apr 13;467(1):21-30. doi: 10.1016/s1383-5718(00)00022-x.
Carcinogenesis in the upper aerodigestive tract is influenced by multiple factors. Besides tobacco and alcohol consumption, specific pollutants such as phthalates, nitrosamines, and polycyclic aromatic carbohydrates may be important in tumor initiation. Genetic factors related to mutagen sensitivity and DNA repair capacity also play a role. The aim of this study was to investigate whether human peripheral blood lymphocytes and mucosal epithelium of the upper aerodigestive tract, the target for volatile and liquid xenobiotics, are equally sensitive to genotoxic agents. The Comet assay was used to detect for DNA damage induced by genotoxic agents in mucosal epithelial cells and peripheral blood lymphocytes of 60 volunteers. Mucosa was harvested from larynx, oropharynx, and inferior nasal turbinates. Xenobiotics investigated were dibutylphthalate (DBP), diisobutylphthalate (DiBP), N'-nitrosodiethylamine (NDELA), benzo[a]pyrene (B[a]P), and N'-methyl-N'-nitro-N-nitrosoguanidine (MNNG). DBP, DiBP, B[a]P, NDELA and MNNG induced a significant increase in DNA migration in both cell populations. Peripheral blood lymphocytes were more sensitive than mucosal cells to DBP and DiBP, but not to NDELA and B[a]P. The correlation, in terms of DNA migration, between lymphocytes and mucosal cells among volunteers was relatively poor. Based on the poor correlation in response between the two cell types, the sensitivity of peripheral blood lymphocytes to genotoxic agents appears to be a poor predictor of sensitivity in the target cells of the upper aerodigestive tract. Further attention should be focused on intra-individual mutagen sensitivities and inter-individual genetic differences as regards susceptibility to upper aerodigestive tract cancer.
上呼吸道和消化道的致癌作用受多种因素影响。除了吸烟和饮酒外,特定污染物如邻苯二甲酸盐、亚硝胺和多环芳烃碳水化合物在肿瘤起始过程中可能也很重要。与诱变敏感性和DNA修复能力相关的遗传因素也发挥作用。本研究的目的是调查人类外周血淋巴细胞和上呼吸道和消化道的黏膜上皮(挥发性和液态异生物素的靶标)对遗传毒性剂是否同样敏感。采用彗星试验检测60名志愿者黏膜上皮细胞和外周血淋巴细胞中遗传毒性剂诱导的DNA损伤。从喉、口咽和下鼻甲采集黏膜。所研究的异生物素包括邻苯二甲酸二丁酯(DBP)、邻苯二甲酸二异丁酯(DiBP)、N'-亚硝基二乙胺(NDELA)、苯并[a]芘(B[a]P)和N'-甲基-N'-硝基-N-亚硝基胍(MNNG)。DBP、DiBP、B[a]P、NDELA和MNNG均导致两种细胞群体中的DNA迁移显著增加。外周血淋巴细胞对DBP和DiBP比黏膜细胞更敏感,但对NDELA和B[a]P则不然。志愿者中淋巴细胞和黏膜细胞之间在DNA迁移方面的相关性相对较差。基于两种细胞类型之间反应的相关性较差,外周血淋巴细胞对遗传毒性剂的敏感性似乎不能很好地预测上呼吸道和消化道靶细胞的敏感性。应进一步关注个体内部的诱变敏感性以及个体之间在上呼吸道和消化道癌症易感性方面的遗传差异。