title: 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.
abstract: We previously described an enhanced sensitivity for cell killing and G(1)-phase cell cycle arrest after acute gamma 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) (137)Cs gamma 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 approximately 3.1 and 4.7 cGy/h for the Coriell control strains with normal radiosensitivity and approximately 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-dose-rate 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.
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523, USA. wilson208@llnl.gov
authors.forename: Paul F
authors.initials: PF
authors.lastname: Wilson
authors.forename: Hatsumi
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Christy L
authors.initials: CL
authors.lastname: Warner
authors.forename: Markus M
authors.initials: MM
authors.lastname: Fitzek
authors.forename: John B
authors.initials: JB
authors.lastname: Little
authors.forename: Joel S
authors.initials: JS
authors.lastname: Bedford
mesh_terms: D000328:Adult; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts; D006262:Health; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D011836:Radiation Tolerance; D012175:Retinoblastoma / Q000473:pathology*