Energy Deposition leads to Increase, Chromosomal aberrations

Modulating Factor 

Details 

Effects on the KER 

References 

Sex 

Females 

Females were found to have increased aberrant cells and chromosome breaks relative to males. 

Maffei et al., 2004 

Age 

Increased or decreased age 

Increases in age were associated with increased CAs. However, it has also been found that young organisms are more sensitive to radiation. One possible explanation for this is that dividing cells are more radiosensitive than those that are quiescent. 

Blakely, 2012; Santovito et al., 2013; Vellingiri et al., 2014 

Smoking 

Smoking status 

Smoking was found to increase chromosomal damage. Chromosome breaks were found to be significantly increased in smokers relative to non-smokers. Likewise, blood samples from smokers that were exposed to radon gas had lymphocytes with significantly increased dicentric aberrations, acentric fragments, chromatid breaks, MN, and NPBs relative to lymphocytes from non-smokers also exposed to radon gas. 

Maffei et al., 2004; Meenakshi and Mohankumar 2013; Meenakshi et al., 2017 

Hyperthermia 

Increased temperature 

In cells exposed to hyperthermic conditions (41°C for 1 h) followed by radiation (4 Gy), there were significant increases in chromosomal translocations and chromosomal fragments at 1 and at 24 h post-exposure, respectively, as compared to cells exposed only to radiation. 

Bergs et al., 2016 

DNA ligase IV 

Presence 

DNA ligase IV helps prevent DNA degradation and increase accurate DNA rejoining, therefore decreasing chromosome breaks and radiation-induced MN. 

Smith et al., 2003; Foray et al., 2016 

Genetic syndromes 

Cockayne syndrome, AT-like disorder, Nijmegen breakage syndrome, Bloom’s syndrome, xeroderma pigmentosum, Fanconi anemia, and ataxia telangiectasia 

The presence of one of these conditions can increase the number of CAs. 

Bender et al., 1988; Foray et al., 2016 

Antioxidants or antigenotoxic agents 

Increased concentration, examples include dimethyl sulfoxide (DMSO) 

The compounds can help decrease the frequency of CAs after irradiation. 

Yang, 1999; Kim and Lee, 2007 

Reference 

Experiment Description 

Result 

Suto et al., 2015 

In vitro. Human peripheral blood lymphocytes were exposed to 60Co γ-rays at 0 – 300 mGy and 5 mGy/sec. The number of dicentrics and translocations in chromosomes 1, 2, and 4 were determined using three differentially colored chromosome painting probes. 

Study of human peripheral blood lymphocytes from a healthy donor subjected to γ-ray radiation in the dose (D) range of 0 - 300 mGy found a calculated CA rate (y) of dicentrics, translocations and dicentrics+translocations (of the quadratic form, y = a + bD + bD^2) found - dicentrics + translocations (a,b,c := 0.0023 ± 0.0003, 0.0015 ± 0.0058, 0.0819 ± 0.0225), dicentrics (a,b,c := 0.0004 ± 0.0001, 0.0008 ± 0.0028, 0.0398 ± 0.0117), translocations (a,b,c := 0.0019 ± 0.0003, 0.0008 ± 0.0028, 0.0398 ± 0.0117). 

Abe et al., 2018 

In vitro. Human mononuclear blood cells from five donors (four males aged 23, 35, 44, and 55 years old, and a 33-year-old female) were exposed to 60Co γ-rays at 0 – 1000 mGy. The dose rate in the irradiator was 26.6 mGy/min with an additional 6.42 mGy to the sample while entering and leaving the irradiation source. None of the subjects had a history of radiotherapy, smoking, or chemotherapy. The number of dicentrics and translocations in chromosomes 1, 2, and 4 were determined using Giemsa staining and Centromere-FISH staining. 

Study of human mononuclear blood cells from healthy donors; analyzed for dicentric chromosomes. Exposure to γ-ray doses (D) in the 0 - 1000 mGy range. Quadratic form fit for the CA rate in Giemsa staining and Centromere-FISH staining cases (y) (of the form y = a + bD + cD^2) found to be: Giemsa staining: (a,b,c := 0.0013 ± 0.0005, 0.0067 ± 0.0071, 0.0313 ± 0.0091), Centromere-FISH staining (a,b,c := 0.0010 ± 0.0004, 0.0186 ± 0.0081, 0.0329 ± 0.0104). Study of mononuclear blood cells from healthy donors; analyzed for translocations. Exposure to γ-ray doses (D) in the 0 - 1000 mGy range. Quadratic form fit for the CA rate (y) before and after donor age adjustment (of the form y = a + bD + cD^2) found to be: before donor age adjustment: (a,b,c := 0.0053 ± 0.0009, 0.259 ± 0.0127, 0.0826 ± 0.0161), after donor age adjustment (a,b,c := 0.0015 ± 0.0009, 0.0049 ± 0.0155, 0.1033 ± 0.0223). 

Jang et al., 2019 

In vitro. Human peripheral blood lymphocytes from four different donors (two males, 36 and 22 years old, and two females, 28 and 24 years old) were exposed to 6 MV X-rays at 0-5 Gy and 0.5 Gy/min. None of the subjects had a history of chemotherapy, smoking, or radiotherapy. The number of dicentrics and translocations in chromosomes 1, 2, and 4 were determined using Giemsa staining and chromosome painting, respectively. 

Human peripheral blood lymphocytes studied from healthy donors. Lymphocytes irradiated with X-rays in a dose (D) range 0 - 5 Gy. Calculated CA rate from dicentrics or translocations (y) (of the form y = a + bD + cD^2). Dicentrics, (a,b,c := 0.0011 ± 0.0004, 0.0119 ± 0.0032, 0.0617 ± 0.0019). Translocations, (a,b,c := 0.0015 ± 0.0004, 0.0048 ± 0.0024, 0.0237 ± 0.0014). 

Schmid et al., 2002 

In vitro. Human peripheral blood lymphocytes from one male donor were exposed to 29 kV X-rays at 0.115 – 2.194 Gy and at 0.009 – 0.140 Gy/min. CAs were determined with fluorescence plus Giemsa staining. 

Study of various X- and γ-ray types irradiating peripheral human blood lymphocytes, analyzed dicentrics and acentrics (10, 29, 60, 220 kV X-rays & Cs-137, Co-60 γ-rays). See Schmid et al. (2002) for details on equations. 

George et al., 2009 

In vitro. HF19 normal primary lung fibroblasts, AT primary fibroblasts, NSB1-deficient primary fibroblasts, M059K glioblastoma cells, and M059J glioblastoma cells were exposed to iron nuclei (1000 MeV/nucleon, 0.2 – 0.5 Gy/min, average LET of 151 keV/um), and 137Cs γ-rays (0.2 – 1 Gy/min) at 0 – 3 Gy. CAs in chromosomes 1, 2, 4, and 11 were determined using FISH staining. 

γ-rays and iron nuclei irradiating HF19 normal primary lung fibroblasts; Ataxia telangiectasia (AT) primary fibroblasts; NSB1-deficient primary fibroblasts (Nijmegen breakage syndrome); M059K glioblastoma cells & M059J glioblastoma cells (lack DNA-dependent protein kinase activity). Dose range of 0 - 3 Gy. See Table 5 & 6 of George et al. (2009) for details on equations. 

Wolf et al. 2008 

In vivo. Female, C57BL/6 mice received head-only exposure to 11 Gy soft X-rays. Mice were either 2 or 26 months-old at irradiation. 6 were irradiated and 6 were non-irradiated controls. Chromosomal aberrations were detected using Wright-trypsin G-banding. 

Irradiation of eight-week-old mice with 11 Gy of X-rays increased the number of abnormal chromosomes from 15 (control) to 27. Irradiation of 26-month-old mice with 11 Gy of X-rays increased the number of abnormal chromosomes from 0 (control) to 30). However, the significance of these results was not indicated. 

Williams et al., 1999 

In vitro. Human lymphocyte cells were exposed to Fe ions (0 – 1 Gy, 1 GeV incident energy), 137Cs photons (0 – 7.5 Gy, 83 cGy/min), and protons (5 Gy, 250 keV incident energy). Chromosomal aberrations were identified using Leishman’s stain. 

CAs rose from 0 to 0.001, 0.004, 0.014, and 0.017 after exposure to 1 Gy 137Cs, 1 Gy Fe, 5 Gy 137Cs, and 5 Gy energetic photons respectively. 

Evans et al., 2001 

In vitro. TK6 and WTK1 human lymphoblastoid cells were exposed to 56Fe ions (0 – 2.25 Gy, 1087 MeV/nucleon) and 137Cs γ-rays (0 – 4 Gy, 0.87 – 0.92 Gy/min). CAs were assessed using Giemsa staining. 

Exposure to higher doses resulted in increased amounts of aberrant cells. For example, in TK6 cells after 56Fe irradiation, 0% of cells were aberrant in the control, 19% were aberrant after 0.63 Gy, and 66% were aberrant after 2.25 Gy. Additionally, 56Fe ions induced increased numbers of aberrant cells when compared to 137Cs γ-rays. 

Hande et al., 2005 

In vivo. Lymphocytes from 31 Russian reactor and plutonium workers were exposed to plutonium ions and γ-rays. Highly exposed plutonium workers received 1.1 Gy of Pu and 1.5 Gy of γ-rays. Moderately exposed plutonium workers received 0.19 Gy of Pu and 0.19 Gy of γ-rays. Reactor workers received only 2.3 Gy of γ-rays. Values are averages. CAs were detected using the mFISH assay. 

The amount of interchromosomal complex translocations were 2.9, 0.23, and 0.21% higher than controls in workers highly exposed, moderately exposed, and exposed to only γ-rays, respectively. 

The amount of interchromosomal simple translocations were 5.1, 1.5, and 4% higher than controls in workers highly exposed, moderately exposed, and exposed to only γ-rays, respectively. 

Durante et al., 1998 

In vitro. Human male lymphocyte cells were exposed to carbon ions (5 Gy, 290 meV/nucleon, 42 keV/μm), neon ions (7 Gy, 400 MeV/nucleon, 31 keV/μm), hydrogen ions (1, 3, 5, 7 Gy, 0.4 keV/μm), and iron ions (0.5, 0.75, 1, 2, Gy, 1000 MeV/nucleon, 140 keV/μm). Chromosomal aberrations were detected using DAPI-counterstaining the PAINT classification. 

As the dose increased from 0 to 7 Gy, the number of DNA breaks per human male lymphocyte cell also increased from 0 to 1.2. This included data using iron ions, hydrogen ions, carbon, and neon. 

Tao et al., 1994 

In vivo. 90 – 110-day old B6CF1/Anl mice received irradiation to the anterior 2/3 of the body with 60Co γ-rays (10 – 40 cGy), 20Ne (670 MeV/amu, 25 keV/um), 56Fe (600 MeV/amu, 193 keV/um), 93Nb (600 MeV/amu, 464 keV/um), 139La (593 MeV/um, 953 keV/um). All stressors except 60Co delivered 10, 20, 40, 80, 160, and 320 cGy. Doses were delivered to the anterior 2/3 of the body. CAs were detected using a modified Feulgen method 64 weeks post-exposure. 

Mouse lenses exposed to all radiation types showed increased MN number per whole mount at increasing doses from 10 to 160 cGy. For example, irradiation from 56Fe particles led to a MN number of 10 after 10 cGy and an MN number of 100 after 160 cGy. 

Bains et al., 2019 

In vitro. Human LECs were exposed to X-rays at 0, 0.001, 0.01, 0.02, 0.1, 1, and 2 Gy. Doses of 0.1, 1.0, and 2.0 had a dose rate of 0.58 Gy/min. 0.001, 0.01 and 0.02 Gy at 0.022 Gy/min. The γ-H2AX assay was used to determine the number of telomere dysfunction induced foci (TIF). 

At 30 min after irradiation, the number of TIF/human lens epithelial cell remained almost 0 after exposure to 0, 0.001, and 0.01 Gy. It then rose quickly to 4.75 TIF/cell at 2 Gy. 

Udroiu et al., 2020 

In vitro. Human LECs were exposed to X-rays at 25, 51.25, 135, 235, and 300 mGy at 0.51, 0.15, and 0.228 Gy/min. The micronuclei frequency was measured with a cytokinesis-blocked micronucleus assay. 

 In human LECs exposed to 25 – 300 mGy the micronuclei frequency increased steadily, reaching 2.4x control at the maximum dose. 

Dalke et al., 2018 

In vivo. 10-week-old, mixed sex B6C3F1 and B6RCF1 hybrid mice received whole-body exposure to 0.063, 0.125, and 0.5 Gy 60Co γ-rays at 0.063 Gy/min. CAs were assessed using Giemsa staining. 

In heterozygous Ercc2 mutants, 12 months after irradiation, the number of aberrations/cell rose from 0.1 (control) to 0.82 (0.5 Gy). There was also a slightly smaller increase after 18 months where the number of chromosomal aberrations/cell rose from 0.1 (control) to 0.3 (0.5 Gy). In wild type mice the largest increase occurred after 12 months where the number of aberrations/cell rose from 0.12 (control) to 0.32 (0.5 Gy). 

Reference 

Experiment Description 

Result 

Tucker et al., 2004 

In vivo. 7-week-old female C57BL/6 mice transgenic for lacZ received whole-body exposure to 1 Gy of 26Fe ions at 1 Gy/min. Aberrations on chromosomes 1, 2, 3, and 8 were determined with a FISH assay. 

Lymphocytes from mice exposed immediately to 1 Gy of iron ions had 19 translocations per 100 cells, 14 acentric fragments per 100 cells, and 10 dicentric chromosomes per 100 cells at 1 week post-irradiation. 

Tao et al., 1994 

In vivo. 90 – 110-day old B6CF1/Anl mice received irradiation to the anterior 2/3 of the body with 60Co γ-rays (10 – 40 cGy), 20Ne (670 MeV/amu, 25 keV/um), 56Fe (600 MeV/amu, 193 keV/um), 93Nb (600 MeV/amu, 464 keV/um), 139La (593 MeV/um, 953 keV/um). All stressors except 60Co delivered 10, 20, 40, 80, 160, and 320 cGy. Doses were delivered to the anterior 2/3 of the body. CAs were detected using a modified Feulgen method. 

Mouse lenses exposed immediately to all radiation types showed increased MN number per whole mount at increasing doses from 10 to 160 cGy at 64 weeks post-irradiation. For example, irradiation from 56Fe particles led to a MN number of 10 after 10 cGy and an MN number of 100 after 160 cGy at 64 weeks post-irradiation. 

Tao et al., 1993 

In vivo. 90 – 110-day old female B6CF mice received irradiation to the anterior 2/3 of the body with 10, 20, 40, 80, 160, and 320 cGy of protons: 250 MeV, LET 0.4 keV/um. 20Ne: 670 MeV/amu, LET 25 keV/um. 56Fe: 600 MeV/amu, LET 183 keV/um. 56Fe: 350 MeV/amu, LET 219 keV/um. 93Nb: 600 MeV/amu, LET 464 keV/um. 139La: 593 MeV/amu, 953 keV/amu. Fragmented nuclei (FN) and MN were detected using a modified Feulgen staining method or haematoxylin and eosin staining. 

In mice immediately irradiated with iron ions, the number of FN in the whole mount of lens cells increased from 1.5 FN (control) to 11 FN at 160 cGy after 64 weeks. The number of FN in the meridional rows increased from 0 (control) to 6 FN at 160 cGy after 64 weeks as well. The number of MN on the whole mount also increased from 0 to 100 at 160 cGy after 64 weeks. Similar changes were also observed with the other radiation types. 

Belkacémi et al., 2001 

In vitro. Bovine lens cells were exposed to 10 Gy at 2 Gy/min from a linear accelerator. The Hoechst 33342 fluorescence was used to measure chromosomal aberrations. 

In lens cells immediately irradiated with X-rays, Hoechst 33342 fluorescence increased 13%, 25%, and 32% above controls at 24, 72, and 96 h post-irradiation, respectively. 

Bains et al., 2019 

In vitro. Human LECs were exposed to X-rays at 0, 0.001, 0.01, 0.02, 0.1, 1, and 2 Gy. Doses of 0.1, 1.0, and 2.0 had a dose rate of 0.58 Gy/min. 0.001, 0.01 and 0.02 Gy at 0.022 Gy/min.  

 In human LECs immediately exposed in vitro to 0.02 Gy, the number of telomere dysfunction-induced foci (TIF)/cell increased to 3x control 30 min post-irradiation. 

Dalke et al., 2018 

In vivo. 10-week-old, mixed sex B6C3F1 and B6RCF1 hybrid mice received whole-body exposure to 0.063, 0.125, and 0.5 Gy 60Co γ-rays at 0.063 Gy/min. CAs were assessed using Giemsa staining. 

In mice immediately exposed to 0.125-0.5 Gy of γ-rays, CAs were observed after 12 months, increasing to a maximum of 0.82 CAs/cell at 0.5 Gy.