Radiation sensitivity of primary fibroblasts from hereditary retinoblastoma family members and some apparently normal controls

Colony formation ability during continuous low-dose-rate gamma irradiation

Paul F. Wilson, Hatsumi Nagasawa, Christy L. Warner, Markus M. Fitzek, John B. Little, Joel S. Bedford

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We previously described an enhanced sensitivity for cell killing and G1-phase cell cycle arrest after acute γ irradiation in primary fibroblast strains derived from 14 hereditary-type retinoblastoma family members (both affected RB1+/- probands and unaffected RB1+/+ parents) as well as distinctive gene expression profiles in unirradiated cultures by microarray analyses. In the present study, we measured the colony formation ability of these cells after exposure to continuous low-dose-rate (0.5-8.4 cGy/h) 137Cs γ radiation for a 2-week growth period. Fibroblasts from all RB family members (irrespective of RB1 genotype) and from 5 of 18 apparently normal Coriell cell bank controls were significantly more radiosensitive than the remaining apparently normal controls. The average dose rates required to reduce relative survival to 10% and 1% were ∼3.1 and 4.7 cGy/h for the Coriell control strains with normal radiosensitivity and ∼1.4 and 2.5 cGy/h for the radiosensitive RB family member and remaining apparently normal Coriell control strains. The finding that a significant proportion of fibroblast strains derived from apparently normal individuals are sensitive to chronic low-doserate irradiation indicates such individuals may harbor hypomorphic genetic variants in genomic maintenance and/or DNA repair genes that may likewise predispose them or their children to cancer.

Original languageEnglish (US)
Pages (from-to)483-494
Number of pages12
JournalRadiation Research
Volume169
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

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Aptitude
Retinoblastoma
Radiation Tolerance
fibroblasts
gamma radiation
Fibroblasts
dosage
irradiation
radiation
G1 Phase Cell Cycle Checkpoints
G1 Phase
maintenance and repair
Microarray Analysis
Transcriptome
DNA Repair
harbors
gene expression
cells
radiation tolerance
DNA repair

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Radiation sensitivity of primary fibroblasts from hereditary retinoblastoma family members and some apparently normal controls : Colony formation ability during continuous low-dose-rate gamma irradiation. / Wilson, Paul F.; Nagasawa, Hatsumi; Warner, Christy L.; Fitzek, Markus M.; Little, John B.; Bedford, Joel S.

In: Radiation Research, Vol. 169, No. 5, 05.2008, p. 483-494.

Research output: Contribution to journalArticle

Wilson, Paul F. ; Nagasawa, Hatsumi ; Warner, Christy L. ; Fitzek, Markus M. ; Little, John B. ; Bedford, Joel S. / Radiation sensitivity of primary fibroblasts from hereditary retinoblastoma family members and some apparently normal controls : Colony formation ability during continuous low-dose-rate gamma irradiation. In: Radiation Research. 2008 ; Vol. 169, No. 5. pp. 483-494.
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