• Nuclear Engineering and Technology
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• v.13 no.3
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• pp.161-167
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• 1981

For determination of mutation frequency induced by chronic irradiation of low dose gamma rays, Tradescarrfia clone 4430 was exposed to Co-60 ${\gamma}$ rays with different exposure rates from 3.6mR/day to 182R/day in or out of the Gamma Field at Kumkok Experiment Farm of KAERI. Somatic mutations based on pink mutant events of the stamen hair cells were clearly observed by the treatment. The pink mutant events were increased proportionally with increasing exposure rates of gamma ray except for relatively high dose rates of 105 R/day and 182 R/day, indicating saturation effect of mutation. The somatic pink mutations could be fairly detectable even in the low dose rate of 3.6mR/day. Therefore, this stamen hair system of Tradescantia clone 4430 seemed to be an reasonable test system for detecting mutability of low level irradiation. These results imply that artificial mutation induction in the fruit and ornamental trees could be expected in the ${\gamma}$-field.

• Korean Journal of Medicinal Crop Science
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• v.3 no.1
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• pp.50-55
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• 1995

This study was conducted to determine the optimum conditions for induction and different somatic of somatic embryos as well as germination of encapsulated and stored somatic embryos. Somatic embryos was better formed in 1/2X MS medium than full - strength MS medium. 0.1 to 1.0mg/lBA and kinetin promoted shoot differentiation of somatic embryos. Higher concentration tend to inhibit differentiation. IAA affect positively both root and shoot growth. In vitro germination of somatic embryos encapsulated with 2% alginate matrix containing 1/2 MS nutrient medium and $AgNO_3$ 5mg/l was 86%. Storage of somatic embryos was effecive at $5^{\circ}C$ but the germination rate decreased with longer storage period. RAPD analyses with plants regenerated from the somatic embryos showed DNA polymorphism, indicating abolition of primer binding site by point mutation, deletion, or insertion of certain sequences.

• Genomics & Informatics
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• v.16 no.2
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• pp.30-35
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• 2018

Patient-derived xenograft (PDX) models are useful tools for tumor biology research and testing the efficacy of candidate anticancer drugs targeting the druggable mutations identified in tumor tissue. However, it is still unknown how much of the genetic alterations identified in primary tumors are consistently detected in tumor tissues in the PDX model. In this study, we analyzed the genetic alterations of three primary colorectal cancers (CRCs) and matched xenograft tissues in PDX models using a next-generation sequencing cancer panel. Of the 17 somatic mutations identified from the three CRCs, 14 (82.4%) were consistently identified in both primary and xenograft tumors. The other three mutations identified in the primary tumor were not detected in the xenograft tumor tissue. There was no newly identified mutation in the xenograft tumor tissues. In addition to the somatic mutations, the copy number alteration profiles were also largely consistent between the primary tumor and xenograft tissue. All of these data suggest that the PDX tumor model preserves the majority of the key mutations detected in the primary tumor site. This study provides evidence that the PDX model is useful for testing targeted therapies in the clinical field and research on precision medicine.

• Journal of Food Hygiene and Safety
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• v.13 no.2
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• pp.135-142
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• 1998

The mutagenicity of three external colorants, lake red CBA (D&C Red No.9, R-9), rhodamine B stearate (D&C Red No.37, R-37) and permanent orange (D&C Orange No.17, O-17) was evaluated. In this study, the genetic toxicity of the these dyes was examined by in vitro chromosome aberration test in cultured mammalian cells, in vivo micronucleus test in ddY mice, and somatic mutation and recombination test (SMART) in Drosophila melanogaster. Three dyes did not induce mutagenicity in chromosome aberration test and micronucleus test. But Red No.9 and Red No. 37 showed slight increase of abnormal wing spots in Drosophila melanogaster.

• Korean Journal of Radiology
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• v.22 no.12
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• pp.1996-2005
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• 2021

Objective: To investigate the multidetector computed tomography (MDCT) features of fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) with germline or somatic mutations, and compare them with those of papillary type II RCC (pRCC type II). Materials and Methods: A total of 24 patients (mean ± standard deviation, 40.4 ± 14.7 years) with pathologically confirmed FH-deficient RCC (15 with germline and 9 with somatic mutations) and 54 patients (58.6 ± 12.6 years) with pRCC type II were enrolled. The MDCT features were retrospectively reviewed and compared between the two entities and mutation subgroups, and were correlated with the clinicopathological findings. Results: All the lesions were unilateral and single. Compared with pRCC type II, FH-deficient RCC was more prevalent among younger patients (40.4 ± 14.7 vs. 58.6 ± 12.6, p < 0.001) and tended to be larger (8.1 ± 4.1 vs. 5.4 ± 3.2, p = 0.002). Cystic solid patterns were more common in FH-deficient RCC (20/24 vs. 16/54, p < 0.001), with 16 of the 20 (80.0%) cystic solid tumors having showed typical polycystic and thin smooth walls and/or septa, with an eccentric solid component. Lymph node (16/24 vs. 16/54, p = 0.003) and distant (11/24 vs. 3/54, p < 0.001) metastases were more frequent in FH-deficient RCC. FH-deficient RCC and pRCC type II showed similar attenuation in the unenhanced phase. The attenuation in the corticomedullary phase (CMP) (76.3% ± 25.0% vs. 60.2 ± 23.6, p = 0.008) and nephrographic phase (NP) (87.7 ± 20.5, vs. 71.2 ± 23.9, p = 0.004), absolute enhancement in CMP (39.0 ± 24.8 vs. 27.1 ± 22.7, p = 0.001) and NP (50.5 ± 20.5 vs. 38.2 ± 21.9, p = 0.001), and relative enhancement ratio to the renal cortex in CMP (0.35 ± 0.26 vs. 0.24 ± 0.19, p = 0.001) and NP (0.43 ± 0.24 vs. 0.29 ± 0.19, p < 0.001) were significantly higher in FH-deficient RCC. No significant difference was found between the FH germline and somatic mutation subgroups in any of the parameters. Conclusion: The MDCT features of FH-deficient RCC were different from those of pRCC type II, whereas there was no statistical difference between the germline and somatic mutation subgroups. A kidney mass with a cystic solid pattern and metastatic tendency, especially in young patients, should be considered for FH-deficient RCC.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.25-25
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• 2018

The Fukushima Daiichi Nuclear Power Plant accident in March 2011 caused severe radioactive contamination in the surrounding environment. Since the accident, much attention has been paid to the biological and genetic consequences of organism inhabiting the contaminated area. The effect of radiation exposure on genetic mutation rates is little known, especially for low doses and in situ conditions. Evaluating DNA mutation by low levels of radiation dose is difficult due to the rare mutation event and lack of sequence information before the accident. In this study, correlations with air dose levels and somatic DNA mutation rates were evaluated using Next Generation Sequencer for the clonal plant, Phyllostachys edulis. This bamboo is known to spread an identical clone throughout Japan, and it has the advantage that we can compare genetic mutation rate among identical clone growing different air dose levels. We collected 94 samples of P. edulis from 14 sites with air dose rates from $0.04{\sim}7.80{\mu}Gy/h$. Their clonal identity was confirmed by analysis using 24 microsatellite markers, and then, sequences among samples were compared by MIG sequence. The sequence data were obtained from 2,718 loci. About ~200,000 bp sequence (80 bp X 2,718 loci) were obtained for each sample, and this corresponds to about 0.01% of the genome sequence of P. edulis. In these sequences, 442 loci showed polymorphism patterns including recent origin mutation, old mutation, and sequence errors. The number of mutations per sample ranged from 0 to 13, and did not correlate with air dose levels. This result indicated that DNA mutations have not accumulated in P. edulis living in the air doses levels less than $10{\mu}Gy/h$. Our study also suggests that mutation rates can be assessed by selecting an appropriate experimental approach and analyzing with next generation sequencer.

• Journal of Embryo Transfer
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• v.31 no.3
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• pp.179-183
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• 2016

Even though klotho deficiency in mice exhibits multiple aging-like phenotypes, studies using large animal models such as pigs, which have many similarities to humans, have been limited due to the absence of cell lines or animal models. The objective of this study was to generate homozygous klotho knockout porcine cell lines and cloned embryos. A CRISPR sgRNA specific for the klotho gene was designed and sgRNA (targeting exon 3 of klotho) and Cas9 RNPs were transfected into porcine fibroblasts. The transfected fibroblasts were then used for single cell colony formation and 9 single cell-derived colonies were established. In a T7 endonuclease I mutation assay, 5 colonies (#3, #4, #5, #7 and #9) were confirmed as mutated. These 5 colonies were subsequently analyzed by deep sequencing for determination of homozygous mutated colonies and 4 (#3, #4, #5 and #9) from 5 colonies contained homozygous modifications. Somatic cell nuclear transfer was performed to generate homozygous klotho knockout cloned embryos by using one homozygous mutation colony (#9); the cleavage and blastocyst formation rates were 72.0% and 8.3%, respectively. Two cloned embryos derived from a homozygous klotho knockout cell line (#9) were subjected to deep sequencing and they showed the same mutation pattern as the donor cell line. In conclusion, we produced homozygous klotho knockout porcine embryos cloned from genome-edited porcine fibroblasts.

• Journal of Radiation Protection and Research
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• v.22 no.1
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• pp.15-21
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• 1997

In vitro somatic mutation induced by ${\gamma}$-radiation and pentachlorophenol(PCP) which is representative of chemical pollutant was measured at the hypoxanthine-guanine phosphoribosyl transferase(hprt) locus in human T- lymphocytes by a cell cloning assay. Mutant cells were selected by their ability to form a clone in the presence of purine analogue 6-thioguanine. The mutant frequencies by ${\gamma}$-irradiation to a dose of 1.0 Gy, 2.0 Gy and 3.0 Gy were 40%, 400% and 750% higher than those in controls. Significant changes were not observed in mutant frequencies in the 0.2 Gy and 0.5 Gy irradiated groups. When the doses of PCP were 15 ppm, 25 ppm and 50 ppm, the mutant frequencies increased by 30%, 90% and 520%, respectively. No changes were observed in the 10 ppm treated group. Similar types of dose-response relationship were shown in the two different mutagens. Reverse transcriptase/polymerase chain reaction technique(RT/PCR) was needed for the mutation spectrum to discriminate combined exposure to radiation and chemicals.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7149-7152
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• 2014

A large number of epidemiological studies have demonstrated that obesity is a risk factor for several human cancers. Several animal studies using rodents with diet-induced or genetic obesity have also demonstrated that obesity can promote tumor development. However, the effects of obesity on the early stages of carcinogenesis, and especially on the spontaneous occurrence of somatic gene mutations, remain unclear. To investigate the effects of obesity on the rate of spontaneous gene mutations, we performed reporter gene mutation assays in liver, kidney, and colon, organs in which obesity appears to be associated with cancer development on the basis of epidemiological or animal studies, in mice with high fat diet (HFD)-induced obesity. Six-week-old male and female C57BL/6 gpt delta mice were fed HFD or standard diet (STD) for 13 or 26 weeks. At the end of the experiments, reporter gene mutation assays of liver, kidney, and colon were performed. Final body weights and serum leptin levels of male and female mice fed HFD for 13 or 26 weeks were significantly increased compared with corresponding STD-fed groups. Reporter gene mutation assays of liver, kidney, and colon revealed that there were no significant differences in gpt or $Spi^-$ mutant frequencies between STD- and HFD-fed mice in either the 13-week or 26-week groups. These results indicate that HFD treatment and consequent obesity does not appear to influence the spontaneous occurrence of somatic gene mutations.

• Journal of Radiation Protection and Research
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• v.23 no.1
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• pp.17-23
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• 1998

Dose response relationships for one of biological end-points (gene mutation) in somatic cells of Tradescantia 4430 clones were studied using neutrons coming out of a californium-252 isotopic source. And the relative biological effectiveness (RBE) of neutrons in relation to X-rays in the induction of TSH pink mutations was assessed. Inflorescences were irradiated with X-ray from X-ray generator and neutrons from $^{252}Cf$ source. Irradiated cuttings were incubated with aeration in neutrient solution under the controlled condition. For more than 4 weeks after irradiation cell mutations were scored. Pink mutation frequencies were calculated from the pooled data for the peak interval (days 6 to 13 post-irradiation). Somatic cell mutations in TSH showed linear dose response relationships in the range of neutron doses available for the experiment. The RBE values estimated for neutrons in relation to X-rays were in the range 3.1 to 6.8, which were much lower than normally recognized value.