A single low dose of X-rays induces high frequencies of genetic instability (aneuploidy) and heritable damage (apoptosis), dependent on cell type and p53 status.
We harvested and analyzed cells from four different non-transformed cell lines surviving a single X-ray exposure. Evidence of radiation-induced karyotype instability was observed in 100% of C3H 10T1/2 fibroblast clones and 11.3% of V79 fibroblast clones. Heritable damage: predisposition to apoptosis, but not karyotype instability, was induced in TK6 (p53(wt/wt)) and WTK1 (p53(mut/mut)) human B-lymphoblastoid cell clones. The studies indicate: (1) genetic instability and/or heritable damage are induced in cells exposed to radiation at a high frequency, and induction of genetic instability is not limited to morphologically transformed cells [Radiat. Res. 138 (1994) S105; Radiat. Environ. Biophys. 36 (1998) 255]; (2) sensitivity to genetic instability and heritable damage depend on cell type; (3) checkpoint stringency and p53 status significantly influence the frequency of radiation-induced genetic instability and heritable damage; (4) in some cell lines, damage induced by low doses of radiation (below 2 Gy) leads to heritable cytotoxic and genotoxic effects in 100% of cells exposed. The data suggest that mammalian cells misinterpret damage induced by ionizing radiation as if it were a physiological cell signal. This contrasts strongly with the response of mammalian cells to damage induced by other types of DNA-toxic agents where damage-specific repair mechanisms are activated.
Crompton
Nigel E A
NE
Division of Radiation Medicine, Paul Scherrer Institute, CH-5232 Villigen-PSI, Switzerland. nigel.crompton@psi.ch
Shi
Yu-Quan
YQ
Wuergler
Frederich
F
Blattmann
Hans
H
D000782:Aneuploidy; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004247:DNA / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D051379:Mice; D008809:Mice, Inbred C3H; D013997:Time Factors; D014965:X-Rays
D004247:DNA