Journal Article

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.

G Otero, M A Avila, L de la Peña, D Emfietzoglou, J Cansado, G F Popescu and V Notario

in Carcinogenesis

Volume 18, issue 8, pages 1569-1575
Published in print August 1997 | ISSN: 0143-3334
Published online August 1997 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/18.8.1569
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.

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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.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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