Lee H C, Yin P H, Yu T N, Chang Y D, Hsu W C, Kao S Y, Chi C W, Liu T Y, Wei Y H
Department of Biochemistry and Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan, ROC.
Mutat Res. 2001 Jun 27;493(1-2):67-74. doi: 10.1016/s1383-5718(01)00160-7.
Accumulation of mitochondrial DNA (mtDNA) mutations in human tissues has been associated with intrinsic aging and environmental insult. Recently, mtDNA mutations have been detected in various tumors, including head and neck tumors. However, the factors affecting the occurrence and accumulation of mtDNA deletions in tumor tissues are poorly understood. In Taiwan, betel quid chewing is a major risk factor for oral cancer. Using polymerase chain reaction (PCR) techniques, we examined large-scale deletions of mtDNA in 53 pairs of tumor and non-tumor oral tissues from the patients with or without betel quid chewing history. The results revealed that irrespective of the history of betel quid chewing, the incidences of the 4977bp deletion and other deletions of mtDNA were lower in the tumor portion as compared with the non-tumor portion. The average proportions of the 4977bp deleted mtDNA in the tumor tissues of the betel quid chewers and non-betel quid chewers were 13- and 5-fold, respectively, lower than those in the corresponding non-tumor tissues. Moreover, the average proportion of 4977bp deleted mtDNA was significantly higher (P<0.05) in the non-tumor oral tissues of the patients with betel quid chewing history than that of the patients without the history of betel quid chewing. These results suggest that betel quid chewing may increase mtDNA mutation in human oral tissues and that accumulation of mtDNA deletions and subsequent cytoplasmic segregation of these mutations during cell division could be an important contributor to the early phase of oral carcinogenesis.
人类组织中线粒体DNA（mtDNA）突变的积累与内在衰老和环境损伤有关。最近，在包括头颈肿瘤在内的各种肿瘤中都检测到了mtDNA突变。然而，影响肿瘤组织中mtDNA缺失发生和积累的因素却知之甚少。在台湾，嚼槟榔是口腔癌的主要危险因素。我们使用聚合酶链反应（PCR）技术，检测了53对有或无嚼槟榔史患者的肿瘤和非肿瘤口腔组织中mtDNA的大规模缺失情况。结果显示，无论有无嚼槟榔史，与非肿瘤部分相比，肿瘤部分中4977bp缺失及其他mtDNA缺失的发生率更低。嚼槟榔者和非嚼槟榔者肿瘤组织中4977bp缺失的mtDNA平均比例分别比相应非肿瘤组织低13倍和5倍。此外，有嚼槟榔史患者的非肿瘤口腔组织中4977bp缺失的mtDNA平均比例显著高于无嚼槟榔史患者（P<0.05）。这些结果表明，嚼槟榔可能会增加人类口腔组织中的mtDNA突变，并且mtDNA缺失的积累以及这些突变在细胞分裂过程中随后的细胞质分离可能是口腔癌发生早期的一个重要因素。
