Ionizing radiation is a known carcinogen and teratogen. However, the point mutations produced by Ionizing radi ation in mammalian cells have not been fully characterized. Determination of a characteristic spectrum of X-ray Induced mutations in mammalian cells could provide clues to cellular repair processes and could serve as a marker of individual exposure to radiation. Mouse fibroblasts containing in their genome multiple copies of a recoverable λ phage shuttle vector were used to detect and analyze radiation-induced point mutations in the supF mutation reporter gene. Following fractionated doses of ionizing radiation, a unique mutational spectrum notable for a high proportion of T:A→G:C transversions (57%) was found. This pattern was distinct from the spectra of UV-induced and spontaneous mutations detected in the same mouse cell assay system (mainly C:G→T:A transitions). The pre dominance of T:A→G:C transversions and the pattern of mutation hot-spots are consistent with a possible role for polymerase β in the repair of X-ray-damaged DNA. These results may also help to define a distinctive mutational signature of X-ray exposure in mammalian cells.
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The authors thank F.Hutchinson for helpful discussions and N.E.Murray, S.J.Baserga, E.G.Leach, C.MacDonald, A.Earl and EJ.Gunther for assistance. This work was supported by the Charles E.Culpeper Foundation, the Leukemia Society of America and the NIH (ES05775).