• Radiation Oncology Journal
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• 제16권2호
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• pp.115-123
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• 1998

자궁 경부암으로 전 골반에 균일하게 방사선 치료를 받은 3명의 환자들을 대상으로 말초혈액임파구의 염색체이상 빈도를 정기적으로 측정함으로써 반복 피폭에 의한 염색체이상 빈도의 변화양상을 구명하고자 하였다. 방사선 조사전에 채취한 혈액에서 얻은 Ydr 값은 0.0060, 0.0000, 0.0029였다. 방사선량이 증가함에 따라 Ydr 값은 직선적으로 증가하였고 측정치들로부터 구한 선형 회귀식은 $Ydr=7.31{\times}10^{-5}D(cGy)+1.45{\times}10^{-2}$(r2=0.8798)이었다 Qdr(d, r)값도 선량 증가에 따라 직선적으로 증가하는 양상을 보였으며 회귀식은 $Qdr=1.01{\times}10^{-4}D(cGy)+1.04$(r2=0.5912)이었다. 따라서 신체 일부에 방사선을 분할 조사할 경우 일정범위 이하의 방사선량에서는 방사선에 의한 염색체이상의 빈도가 직선적으로 증가함을 알 수 있었다.

• Clinical and Experimental Pediatrics
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• 제46권12호
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• pp.1186-1193
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• 2003

목 적 : 염색체 취약부위는 세포를 특정의 화학물질에 노출시키거나 특수한 배양조건에서 배양 할 때 쉽게 파열되는 염색체상의 특정구역이다. 취약부위는 유전성질환 및 악성종양과 관련이 있으며, 현재에는 분자생물학적 실험기법의 개발로 분자수준에서 이해가 되고 있다. 새로운 취약부위 및 취약부위의 발현을 높이거나 쉽게 관찰할 수 있는 실험실적 조건을 알아보기 위하여 항암제로 사용되는 Ara-C를 이용하여 염색체파열을 조사하여 보았다. 한편 염색체 취약부위가 종양형성과 관련이 있다는 사실에 기초하여 Ara-C에 의해 발열되는 취약부위와 암유전자가 위치하는 부위 및 종양에서 일정하게 염색체변이가 관찰되는 특정의 염색체 부위와의 상관관계도 알아보고자 하였다. 방 법 : 정상 성인 남녀 각각 3명의 말초혈액 내 T-림프구를 세포배양 후 Ara-C를 첨가하고 다시 caffeine을 처리한 뒤 종전에 시행했던 방법과 동일하게 검체 처리하여 염색체파열 부위를 관찰하였다. 염색체 취약부위는 염색체상의 일정부위에서 100개의 염색체파열 당 2회 이상의 염색체파열이 6명 중 4명 이상에서 관찰되는 경우로 정의하였다. 결 과 : 1) T-림프구를 엽산이 부족한 MEN-FA 배지에서 배양 시 Ara-C는 100개의 분열세포 당 252.1개의 염색체파열을 유도하였으며, Ara-C를 처리하지 않은 대조군에서 25.2개가 관찰되어 Ara-C를 처리한 경우에 염색체파열이 의미 있게 많았다(P<0.05). 2) Ara-C에 의한 염색체파열은 엽산이 부족한 MEM-FA 배지에서 엽산이 충분한 RPMI 1640 배지에서 보다 많이 되었다(P<0.05). 한편, 2.0 mM 농도의 caffeine은 엽산만 부족한 배양 배지에서는 염색체파열을 상승시키지 못했으나, Ara-C와 병행사용 시 상승시켰다. 3) Ara-C에 의해 가장 많이 파열된 부위는 3p14.2.이었으며, 발현된 취약부위는 20부위였다. 4) 발현된 취약부위 중 7 부위는 JUN, SKI, REL, N-MYC, FHIT, MET, ETS-1, FOS의 암유전자가 위치하는 부위와 일치하였으며, 15부위는 급성림프구성백혈병, 급성골수성백혈병, 만성림프구성백혈병, 골수이형성성증, 악성흑색종, 신경모세포종, 소세포성폐암, 난소암, 유전성 신장암, 혼합성 지방육종시 염색체상에 이상이 있는 부위와 일치하였다. 결 론 : S기 특이성 항암제인 Ara-C는 정상성인의 T-림프구를 엽산이 부족한 MEM-FA배지에서 배양시 염색체 파열을 대조군에 비해 의미 있게 유도하였다. 한편으로 Ara-C 특이성 염색체 취약부위는 암유전자가 위치하는 부위 및 특정 종양에서 관찰되는 특이한 염색체변이가 있는 부위와 상당 예에서 일치하여 아직 알려지지 않은 암유전자를 찾거나 분석하는데 기초적인 자료를 제공할 뿐 아니라 염색체변화와 종양형성과정의 상관관계를 이해하는데 도움이 될 것으로 사료된다.

• Asian-Australasian Journal of Animal Sciences
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• 제17권10호
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• pp.1329-1333
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• 2004

To isolate the microsatellites from the chromosomal DNA of the Korean cattle (Hanwoo) and to use those for the genetic selection, four bacteriophage genomic libraries containing the chromosomal DNA of six Hanwoo steers showing the differences in meat quality and quantity were used. Screening of the genomic libraries using $^{32}P-radiolabeled 5'-({CA})_{12}-3$nucleotide as a probe, resulted in isolation of about 3,000 positive candidate bacteriophage clones that contain $(CA)_n$-type dinucleotide microsatellites. After confirming the presence of microsatellite in each positive candidate clone by Southern blot analysis, the DNA fragments that include microsatellite and flanking sequences possessing less than 2 kb in size, were subcloned into plasmid vector. Results from the analysis of microsatellite length polymorphism, using twenty-two PCR primers designed from flanking region of each microsatellite DNA, demonstrated that 208 and 210 alleles of HW-YU-MS#3 were closely related to the economic traits such as marbling score, daily gain, backfat thickness and M. longissimus dorsi area in Hanwoo. Interestingly, HW-YU-MS#3 microsatellite was localized in bovine chromosome 17 on which QTLs related to regulation of the body fat content and muscle ypertrophy locus are previously known to exist. Taken together, the results from the present study suggest the possible use of the two alleles as a DNA marker related to economic trait to select the Hanwoo in the future.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7343-7350
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• 2015

Genetic changes associated with acute lymphoblastic leukemia (ALL) provide very important diagnostic and prognostic information with a direct impact on patient management. Detection of chromosome abnormalities by conventional cytogenetics combined with fluorescence in situ hybridization (FISH) play a very significant role in assessing risk stratification. Identification of specific chromosome abnormalities has led to the recognition of genetic subgroups based on reciprocal translocations, deletions and modal number in B or T-cell ALL. In the last twelve years 102 newly diagnosed childhood/adult ALL bone marrow samples were analysed for chromosomal abnormalities with conventional G-banding, and FISH (selected cases) using specific probes in our hospital. G-banded karyotype analysis found clonal numerical and/or structural chromosomal aberrations in 74.2% of cases. Patients with pseudodiploidy represented the most frequent group (38.7%) followed by high hyperdiploidy group (12.9%), low hyperdiploidy group (9.7%), hypodiploidy (<46) group (9.7%) and high hypertriploidy group (3.2%). The highest observed numerical chromosomal alteration was high hyperdiploidy (12.9%) with abnormal karyotypes while abnormal 12p (7.5%) was the highest observed structural abnormality followed by t(12;21)(p13.3;q22) resulting in ETV6/RUNX1 fusion (5.4%) and t(9;22)(q34.1;q11.2) resulting in BCR/ABL1 fusion (4.3%). Interestingly, we identified 16 cases with rare and complex structural aberrations. Application of the FISH technique produced major improvements in the sensitivity and accuracy of cytogenetic analysis with ALL patients. In conclusion it confirmed heterogeneity of ALL by identifying various recurrent chromosomal aberrations along with non-specific rearrangements and their association with specific immunophenotypes. This study pool is representative of paediatric/adult ALL patients in Oman.

• 한국환경성돌연변이발암원학회지
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• 제21권2호
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• pp.99-105
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• 2001

Sophoricoside was isolated as the inhibitor of IL-5 bioactivity from Sophora japonica (Leguminosae). It has been reported to has an anti-inflammatory effect on rat paw edema model. To develope as an anti-allergic drug, genotoxicity of sophoricoside was investigated in bacterial and mammalian cell system such as Ames bacterial reversion test, chromosomal aberration assay and single cell gel electrophoresis (Comet) assay. As results, in the range of 1,250~40 $\mu\textrm{g}$/plate sophoricoside concentrations was not shown significant mutagenic effects in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 strains in Ames test. The 80% cell growth inhibition concentration (IC/SUB 80/) of sophoricoside was determined as above 5,000 $\mu\textrm{g}$/$m\ell$ in Chinese hamster lung (CHL) fibroblast cell and L5178Y mouse lymphoma cell line for the chromosomal aberration and comet assay, respectively. Sophoricoside was not induced chromosomal aberration in CHL fibroblast cell at concentrations of 700, 350 and 175 $\mu\textrm{g}$/$m\ell$ or 600, 300 and 150 $\mu\textrm{g}$/$m\ell$ in the absence or presence of S-9 metabolic activation system, respectively. Also, in the comet assay, the induction of DNA damage was not observed in L5178Y mouse lymphoma cell line both in the absence or presence of S-9 metabolic activation system. From these results, no genotoxic effects of sophoricoside were observed in bacterial and mammalian cell systems used in these experiments.

• Safety and Health at Work
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• 제2권1호
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• pp.17-25
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• 2011

Objectives: In this study, the in vitro mammalian chromosomal aberration (CA) assay was conducted to gain additional information concerning the hazards associated with the use of cyclopentane and ammonium nitrate. While these two chemicals had already been tested by many methods, they had not been studied in the CA test. Methods: The assay was performed using the ovarian infantile cell (CHO-K1 cell), by the direct method (-S9) and by the metabolic activated method (+S9 mix). Results: Using the direct method, the 7 dosages in a 48 hour treatment group did not show that the frequency of CA is proportion to the dosage addition. The frequency of CA is not proportion to the dosage addition for a 6 hour treatment using the metabolic activated method. Conclusion: From these findings, it was decided that the 2 chemicals do not induce chromosomal aberrations under the tested conditions.

• Journal of Genetic Medicine
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• 제12권2호
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• pp.85-91
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• 2015

Purpose: Noninvasive prenatal test (NIPT) by massively parallel sequencing (MPS) of cell-free fetal DNA in maternal plasma marks a significant advancement in prenatal screening, minimizing the need for invasive testing of fetal chromosomal aneuploidies. Here, we report the initial clinical performance of NIPT in Korean pregnant women. Materials and Methods: MPS-based NIPT was performed on 910 cases; 5 mL blood samples were collected and sequenced in the Shenzhen BGI Genomic Laboratory to identify aneuploidies. The risk of fetal aneuploidy was determined by L-score and t-score, and classified as high or low. The NIPT results were validated by karyotyping for the high-risk cases and neonatal follow-up for low-risk cases. Results: NIPT was mainly requested for two clinical indications: abnormal biochemical serum-screening result (54.3%) and advanced maternal age (31.4%). Among 494 cases with abnormal biochemical serum-screening results, NIPT detected only 9 (1.8%) high-risk cases. Sixteen cases (1.8%) of 910 had a high risk for aneuploidy: 8 for trisomy 21, 2 for trisomy 18, 1 for trisomy 13, and 5 for sex chromosome abnormalities. Amniocentesis was performed for 7 of these cases (43.8%). In the karyotyping and neonatal data, no false positive or negative results were observed in our study. Conclusion: MPS-based NIPT detects fetal chromosomal aneuploidies with high accuracy. Introduction of NIPT as into clinical settings could prevent about 98% of unnecessary invasive diagnostic procedures.

• Toxicological Research
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• 제20권1호
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• pp.43-47
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• 2004

In order to investigate the safety of a water extract (ADP) of 1 : 1 mixture of Anemarrhena rhizoma and Phellodendron cortex for alleviating benign prostate hyperplasia, genotoxicity studies in bacterial and mammalian cell assay systems, namely, the Ames bacterial reverse mutation and chromosomal aberration assays were performed. As shown by the results of the Ames bacterial reversion assay, ADP in the range of 625-5000 $\mu\textrm{g}$/plate did not induce mutagenicity in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 strains in the absence or in the presence of S9 (the microsomal fraction of rat liver homogenate) metabolic activation. The $IC_{50}$ (50% cell growth inhibition concentration) values of ADP for the chromosomal aberration assay were determined; these were 2425 $\mu\textrm{g}$/ml in the absence and 8126 $\mu\textrm{g}$/ml in the presence of S9 metabolic activation in Chinese hamster lung (CHL) fibroblast cell culture. No chromosomal aberration was observed in CHL cells treated with ADP at 2425, 1212.5 and 606.25 $\mu\textrm{g}$/ml in the absence, or at 8126, 4063 and 2031.5 $\mu\textrm{g}$/ml in the presence of S9 metabolic activation. These results show that under the conditions used, ADP does not harmfully affect the bacterial or mammalian cell system at the gene level.

• 대한미생물학회지
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• 제19권1호
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• pp.85-108
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• 1984

In order to study the relationship between resistance of tumor cells to anticancer drugs and immunologic cytotoxicity and their chromosome number, a line of cancer cells (NS-1) was exposed to BCNU and CCNU in vitro. Characteristics of the distribution of chromosome number of the survived cells were then comparatively analyzed. Effect of immune mediated cytotoxicity, i.e. complement and cell-mediated cytotoxicity, on the ploidy characteristics was observed in the same way. NS-1 cells were found to be a population of neoplastic cells of heterogeneity having 5 to 115 chromosomes per cell in metaphase. The majority of the cells were belong to the class of chromosome number 56 to 60 which were considered as the stem cell line. Dramatic changes in the distribution of chromosome number following drug treatment were not observed. However the range of chromosome distribution was slightly changed. Characteristics of chromosomal distribution of drug treated cells were not significantly varied by different doses of drug treated. Changed chromosomal distribution patterns of drug treated cells were reversible, especially the cells having 56 to 60 chromosomes recovered rapidly. Cells having 41-60 and 61-80 chromosomes among cells treated with BCNU and cells with 41-60 chromosomes after CCNU treatment were the major population which regenerated continuously. Following BCNU treatment cells having 61-80 chromosomes were not varied much whereas CCNU treatment affects the population in the same class. Chromosomal aberrations were significantly enhanced by BCNU and CCNU treatment. The frequency of chromosomal aberrations was greater in cells having more than 40 chromosomes compared with that in cells having less than 40 chromosomes. Changes in ploidy characteristics of the cells following complement mediated and cell mediated cytotoxicity were not significant. Therefore it was tentatively concluded that association of numerical distribution pattern of NS-1 cells with the response to the treatment used in this experiment was not recognized.

• Journal of Genetic Medicine
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• 제17권1호
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• pp.21-26
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• 2020

Purpose: To evaluate the additive value of prenatal chromosomal microarray analysis (CMA) in assessing increased nuchal translucency (NT) (≥3.5 mm) with normal karyotype and the possibility of detecting clinically significant genomic imbalance, based on specific indications. Materials and Methods: Invasive samples from 494 pregnancies with NT ≥3.5 mm, obtained from the Research Center of Fertility & Genetics of Hamchoon Women's Clinic between January 2019 and February 2020, were included in this study and CMA was performed in addition to a standard karyotype. Results: In total, 494 cases were subjected to both karyotype and CMA analyses. Among these, 199 cases of aneuploidy were excluded. CMA was performed on the remaining 295 cases (59.7%), which showed normal (231/295, 78.3%) or non-significant copy number variation (CNV), such as benign CNV or variants of uncertain clinical significance likely benign (53/295, 18.0%). Clinically significant CNVs were detected in 11 cases (11/295, 3.7%). Conclusion: Prenatal CMA resulted in a 3% to 4% higher CNV diagnosis rate in fetuses exhibiting increased NT (≥3.5 mm) without other ultrasound detected anomalies and normal karyotype. Therefore, we suggest using high resolution, non- targeting CMA to provide valuable additional information for prenatal diagnosis. Further, we recommend that a genetics specialist should be consulted to interpret the information appropriately and provide counseling and follow-up services after prenatal CMA.