tion of genomic instability was assayed as chromosomal aberrations in mammary epithelial cells at 25 population doublings after the cells had been irradiated in vitro or in vivo (Ullrich and Davis 1999), a downward-curving dose-response curve was observed between 0 and 0.25 Gy, with the response saturating between 1 and 3 Gy at about 0.35 aberration per cell. The percentage of CHO clones (containing a human chromosome 4) that were stable for chromosomal translocations in chromosome 4, had a linear dose-response of 3 × 10−5 events per irradiated cell per milligray between 1 and 10 Gy (Limoli and others 1999). For HPRT mutations in CHO cells, the percentage of clones that were unstable for de novo HPRT mutations was 5 × 10−5 events per irradiated cell per milligray, based on 10% being unstable after 2 Gy (Little 1998). Between 4 and 12 Gy, the percentage of unstable clones remained the same at 10–20%. For irradiated human blood lymphocytes stimulated with PHA (phytohemagglutinin) and analyzed 51–57 d after irradiation, the frequency of de novo aberrations was (3 to 10) × 10−5 chromosomal aberrations per cell per milligray (Holmberg and others 1998).
Genomic instability was also observed in mice as gene deletions in melanocytes exposed to X-irradiation (Schiestl and others 1994a), with a threefold increase at 0.01 Gy and a twelvefold increase at 1.0 Gy. The frequency of gene deletions was about 100 times higher than mutation frequencies; therefore, the authors speculated that the deletions resulted from nontargeted effects, such as an increased recombination frequency or genomic instability in the proliferating melanocytes. The dose-response was linear between 0.01 and 1.0 Gy and had a slope of 8 × 10−5 events per cell per milligray. Note that the three values listed above for the frequencies of radiation-induced instability (3–10 × 10−5 events per cell per milligray) are of the same order of magnitude as the frequency of chromosomal aberration induced directly by irradiation (1–4 × 10−5 events per cell per milligray; Table 2-1).
A malignant transformation experiment with primary hamster embryo cells exposed to five different doses from 0.03 to 1.5 Gy yielded a linear dose-response curve that had a slope of 4 × 10−6 transformants per viable cell per milligray (Borek and others 1983). An extensive collaborative study involving six laboratories that quantified malignant transformation of immortalized mouse C3H 10T1/2 cells exposed to