Lack of sensitivity of primary Fanconi's anemia fibroblasts to UV and ionizing radiation.
Clinical observations and theoretical considerations suggest some degree of radiosensitivity in Fanconi's anemia (FA), but experimental evidence remains controversial. We tested the sensitivity of primary skin fibroblast cultures from all known FA complementation groups to ionizing radiation and ultraviolet light using conventional cell growth and colony formation assays. In contrast to previous studies, and because FA fibroblasts grow and clone poorly at ambient oxygen, we performed our sensitivity tests under hypoxic cell culture conditions. Fibroblast strains from healthy donors served as negative controls and those from patients with ataxia telangiectasia (AT) and Cockayne syndrome (CS) as positive controls. We observed interstrain variation but no systematic difference in the response of FA and non-FA control fibroblasts to ionizing radiation. After exposure to UV radiation, only complementation group A, G and D2 strains displayed values for colony formation EC50 that were intermediate between those for the negative and positive controls. Because of considerable interstrain variation, minor alterations of the response of individual FA strains to ionizing and UV radiation should be interpreted with caution and should not be taken as evidence for genotype-specific sensitivities of primary FA fibroblasts. All together, our data indicate neither systematic nor major sensitivities of primary FA fibroblast cultures of any complementation group grown under hypoxic cell culture conditions to ionizing or UV radiation.
Department of Human Genetics, University of Wuerzburg, Biozentrum, Am Hubland, D-97074 Wuerzburg, Germany.
Reinhard
R
Kalb
Michael
M
Duerr
Matthias
M
Wagner
Sabine
S
Herterich
Michaela
M
Gross
Martin
M
Digweed
Hans
H
Joenje
Holger
H
Hoehn
Detlev
D
Schindler
D002455:Cell Division / Q000528:radiation effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004307:Dose-Response Relationship, Radiation; D005199:Fanconi Anemia / Q000473:pathology* / Q000503:physiopathology*; D005347:Fibroblasts / Q000473:pathology* / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D011829:Radiation Dosage; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D014466:Ultraviolet Rays