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 language | English (US) |
|---|---|
| Pages (from-to) | 483-494 |
| Number of pages | 12 |
| Journal | Radiation Research |
| Volume | 169 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2008 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Radiation sensitivity of primary fibroblasts from hereditary retinoblastoma family members and some apparently normal controls
T2 - Colony formation ability during continuous low-dose-rate gamma irradiation
AU - Wilson, Paul F.
AU - Nagasawa, Hatsumi
AU - Warner, Christy L.
AU - Fitzek, Markus M.
AU - Little, John B.
AU - Bedford, Joel S.
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=43449108282&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=43449108282&partnerID=8YFLogxK
U2 - 10.1667/RR1333.1
DO - 10.1667/RR1333.1
M3 - Article
VL - 169
SP - 483
EP - 494
JO - Radiation Research
JF - Radiation Research
SN - 0033-7587
IS - 5
ER -