Altered processing of precursor transcripts and increased levels of the subunit I of mitochondrial cytochrome c oxidase in Syrian hamster fetal cells initiated with ionizing radiation.
Altered processing of precursor transcripts and increased levels of the subunit I of mitochondrial cytochrome c oxidase in Syrian hamster fetal cells initiated with ionizing radiation.
复制标题
电离辐射引发叙利亚仓鼠胎儿细胞中前体转录物的加工过程发生改变，线粒体细胞色素 c 氧化酶 I 亚基水平增加。
DOI：
10.1093/carcin/18.8.1569
复制
发表时间：
1997
期刊：
影响因子：
4.7
通讯作者：
Notario,V
中科院分区：
文献类型：
--
作者：
Otero,G;Avila,MA;delaPeña,L;Emfietzoglou,D;Cansado,J;Popescu,GF;Notario,V
用电离辐射处理叙利亚仓鼠胎儿细胞（SHFC），建立了21个转化细胞系。相对于未辐照的对照组，辐照后早期传代的细胞（p.3）显示出明显的形态学改变，生长速率增加，寿命延长，它们在裸鼠中具有接触抑制作用，并且不具有致瘤性，尽管它们在培养物中延长传代后具有致瘤性（p. > 30）。正常细胞（84-3）和辐射引发的细胞系在早期传代的差异mRNA显示分析表明，后者含有增加的前体（4倍）和成熟（1.7倍）的线粒体（mt）基因编码的细胞色素c氧化酶（CO I）的亚基I的转录物的稳态水平。在57%的辐照（HDR）细胞系中始终观察到这些分子变化，并在连续传代期间稳定维持（p> 50）。对这些细胞系之一（HDR-3）的进一步分析表明，CO I前体转录物的积累是mRNA稳定化和mtDNA复制和/或扩增增加的结果。辐射引发的细胞中含有升高水平的CO I蛋白，细胞色素c氧化酶（CO）的活性降低了75%，和5倍的过氧化氢的浓度增加分泌到他们的培养基中相比，没有改变CO I mRNA加工的细胞。我们的研究结果表明，MT CO I加工的改变可能在电离辐射引起的哺乳动物细胞肿瘤转化中发挥作用。
Treatment of Syrian hamster fetal cells (SHFC) with ionizing radiation resulted in the establishment of 21 transformed cell lines. Relative to unirradiated controls, cells from early post-irradiation passages (p.3) showed marked morphologic alterations, increased growth rate and extended life span, and they were contact-inhibited and not tumorigenic in nude mice, although they became tumorigenic after extended passaging in culture (p. > 30). Differential mRNA display analyses of normal cells (84-3) and radiation-initiated cell lines at early passage showed that the latter contained increased steady-state levels of the precursor (4-fold) and mature (1.7-fold) transcripts of the mitochondrial (mt) gene encoding the subunit I of cytochrome c oxidase (CO I). These molecular alterations were consistently observed in 57% of the irradiated (HDR) cell lines, and were stably maintained during continuous passaging (p. > 50). Further analyses of one of these cell lines (HDR-3) demonstrated that the accumulation of CO I precursor transcripts was the result of mRNA stabilization and increased replication and/or amplification of the mt DNA. Radiation-initiated cells contained elevated levels of the CO I protein, showed a 75% reduction in cytochrome c oxidase (CO) activity, and a 5-fold increase in the concentration of hydrogen peroxide secreted into their culture medium compared with cells with no alterations in CO I mRNA processing. Our findings suggest that alterations in mt CO I processing may play a role in the neoplastic conversion of mammalian cells by ionizing radiation.