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

作者：Otero G; Avila MA; delaPena L; Emfietzoglou D; Cansado J; Popescu GF; Notario V

来源：Carcinogenesis, 1997, 18(8): 1569-1575.

DOI：10.1093/carcin/18.8.1569

Treatment of Syrian hamster fetal cells (SHFC),vith 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 tatter 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 (GO) 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.

• 出版日期1997-8