Carcinogenesis, Vol 18, 1569-1575, Copyright © 1997 by Oxford University Press
G Otero, MA Avila, L de la Pena, D Emfietzoglou, J Cansado, GF Popescu and V Notario
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.
ARTICLES
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
Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.
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