Impaired recovery and mutagenic SOS-like responses in ataxia telangiectasia cells.
Radiosensitive fibroblasts from patients with ataxia telangiectasia (AT) were studied for their proficiency in two putative eukaryotic SOS-like responses, namely the enhanced reactivation (ER) and enhanced mutagenesis of damaged viruses infecting pre-irradiated versus mock-treated cells. A previous report indicated that, unlike normal human cells, a line of AT fibroblasts (AT5BIVA) could not be induced to express ER of damaged parvovirus H-1, a single-stranded DNA virus, by UV- or X-irradiation. In the present study, AT5BIVA fibroblasts were also distinguished from normal cells by the inability of the former to achieve enhanced mutagenesis of damaged H-1 virus upon cell UV-irradiation. In contrast, dose-response and time-course experiments revealed normal levels of ER of Herpes simplex virus 1, a double-stranded DNA virus, in X- or UV-irradiated AT5BIVA cells. Taken together, these data point to a possible deficiency of AT cells in a conditioned mutagenic process that contributes to a greater extent to the recovery of damaged single-stranded than double-stranded DNA. Such a defect may concern the replication of damaged DNA or the generation of signals promoting the latter process and may be related to the lack of radiation-induced delay that is typical of AT cell DNA synthesis.
Hilgers
G
G
Laboratory of Biophysics and Radiobiology, Université Libre de Bruxelles, Rhode-St-Genèse, Belgium.
Abrahams
P J
PJ
Chen
Y Q
YQ
Schouten
R
R
Cornelis
J J
JJ
Lowe
J E
JE
van der Eb
A J
AJ
Rommelaere
J
J
D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000473:pathology; D002461:Cell Line, Transformed; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000528:radiation effects; D006801:Humans; D009154:Mutation; D013014:SOS Response, Genetics / Q000528:radiation effects*; D013539:Simian virus 40; D014965:X-Rays