Pietka Grzegorz, Kukwa Wojciech, Bartnik Ewa, Scińska Anna, Czarnecka Anna M
Instytut Genetyki i Biotechnologii Uniwersytetu Warszawskiego.
Otolaryngol Pol. 2008;62(2):158-64. doi: 10.1016/S0030-6657(08)70233-6.
Data reported until today suggested a pivotal role of nuclear DNA mutations in the process of carcinogenesis. Recently more and more authors claim that disruption of mitochondrial DNA should not be excluded from this analysis. mtDNA have been reported in many cancers of head and neck region. Mitochondrial D-loop has been proven to be mutation hot - spot with majority of mutations in the positions 303 to 315 of poly-C tract. Data show that 37% of patients with premalignant lesions and 62% with carcinoma in situ are positive for mtDNA mutations. Moreover mutations in genes encoding ND2, ND5, COIII, CYTB, and ATP6 were observed in 17% of patients. Mutations in mitochondrial rRNA genes occured in similar number of cases. Neoplastic cells undifferentiation and disease progression is accompanied by multiplication of mtDNA number and increased mtDNA content. mtDNA content corellates with the stage of the disease. mtDNA mutations faciliate cell proliferation and inhibit apoptosis by increasing the production of ractive oxygen species (ROS). Cells harbouring mutated mtDNA have increased proliferation rate, as increased ROS concentration may act as an endogenous growth factor.
截至今日所报告的数据表明,核DNA突变在致癌过程中起关键作用。最近,越来越多的作者认为,在这一分析中不应排除线粒体DNA的破坏。线粒体DNA已在许多头颈部癌症中被报道。线粒体D环已被证明是突变热点,大多数突变发生在多聚C序列的303至315位。数据显示,37%的癌前病变患者和62%的原位癌患者线粒体DNA突变呈阳性。此外,在17%的患者中观察到编码ND2、ND5、COIII、CYTB和ATP6的基因发生突变。线粒体rRNA基因的突变发生情况类似。肿瘤细胞的未分化和疾病进展伴随着线粒体DNA数量的增加和线粒体DNA含量的升高。线粒体DNA含量与疾病阶段相关。线粒体DNA突变通过增加活性氧(ROS)的产生促进细胞增殖并抑制细胞凋亡。携带突变线粒体DNA的细胞增殖率增加,因为ROS浓度升高可能作为一种内源性生长因子。