title: 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.
abstract: 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.
authors.affiliation: Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: G
authors.initials: G
authors.lastname: Otero
authors.forename: M A
authors.initials: MA
authors.lastname: Avila
authors.forename: L
authors.initials: L
authors.lastname: de la Peña
authors.forename: D
authors.initials: D
authors.lastname: Emfietzoglou
authors.forename: J
authors.initials: J
authors.lastname: Cansado
authors.forename: G F
authors.initials: GF
authors.lastname: Popescu
authors.forename: V
authors.initials: V
authors.lastname: Notario
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D017690:Cell Transplantation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006224:Cricetinae; D003576:Electron Transport Complex IV / Q000096:biosynthesis / Q000235:genetics* / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D011498:Protein Precursors / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000528:radiation effects*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D011498:Protein Precursors; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D003576:Electron Transport Complex IV