• Journal of Preventive Medicine and Public Health
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• 제22권1호
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• pp.116-124
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• 1989

일부 중금속에 의한 배양임파구에서 세포유전학적 독성을 알아보고자 $NiCl_2,\;K_2Cr_2O_7CdCl_2$ 및 $HgCl_2$에 의한 SCE빈도 및 염색체이상을 조사한 결과는 다음과 같다. SCE빈도는 공시한 중금속 모두에서 농도증가에 따라 대조군의 $7.20{\pm}2.5$에 비해 유의하게 증가되었으며(p<0.05), 각 중금속의 최고 SCE빈도는 $NiCl_2$의 경우 $1{\times}10^{-4}M$에서 $11.6{\pm}4.0,\;K_2Cr_2O_7$의 경우 $1{\times}10^{-5}M$에서 $16.3{\pm}4.1,\;CdCl_2$의 경우 $1{\times}10^{-6}M$에서 $11.4{\pm}5.5$ 및 $HgCl_2$의 경우 $1{\times}10^{-5}M$에서 $12.6{\pm}5.5$로 나타났다. 또한 공시한 농도에서 가장 높은 SCE유발 중금속은 6가 크롬이었으며 니켈, 카드뮴, 수은은 비교적 낮은 SCE빈도를 보였다. 염색체이상은 gap, break, 기타의 순으로 그 빈도가 감소하였으며 염색체이상을 갖는 세포의 전체빈도는 니켈과 크롬화합물에서는 농도증가에 따라 증가되었고 크롬의 경우 대조군의 2.0%에 비해 $1{\times}10^{-4}M$에서는 15.7%로 가장 높은 염색체이상 빈도를 보였다. 염색체이상 유형별로는 니켈의 경우 염색체 gap은 농도증가에 따라 용량대 반응으로 증가한 반면 break는 유의한 변화가 없었으며 크롬의 경우는 gap과 break가 비슷한 양상으로 증가되었다. 그러나 수은과 카드뮴의 경우에서는 염색체이상이 거의 유발되지 않았다.

• 대한핵의학회지
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• 제27권1호
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• pp.118-122
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• 1993

전이성 분화갑상선암을 치료할 목적으로 사용된 $^{131}I$에 의한 염색체 손상여부를 검정하기 위하여 치료 전후의 자매염색분체교환(SCE)의 빈도 및 말초혈액의 백혈구수를 정상대조군과 환자군에서 조사하였다. 1) 정상인으로 설정한 대조군에 있어서의 자매염색분체교환 빈도수가 $3.8{\pm}0.4$인데 비하여 $^{131}I$ 투여전의 SCE 빈도가 $4.2{\pm}0.7$으로 차이를 보이지 않았다(p=0.17). 2) $^{131}I$ 투여후 2일째 SCE 빈도는 $7.9{\pm}0.8$으로 치료전에 비해 유의하게 증가하였으며 (p<0.001), 9일째에는 $6.4{\pm}0.6$으로 2일째에 비해서는 유의하게 감소하였으나(p=0.002), 치료전에 비해서는 아직도 유의하게 높았다 (P<0.001). 3) 같은 기간동안 백혈구의 수는 유의한 변화를 보이지 않았다. 결과적으로, $^{131}I$ 치료후 염색분체의 손상은 일어나며, 서서히 회복되나 1주일 이내에는 완전한 회복을 보이지 않음을 알 수 있었다.

• BMB Reports
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• 제51권9호
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• pp.437-443
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• 2018

Non-homologous end joining (NHEJ), and to a lesser extent, the error-free pathway known as homology-directed repair (HDR) are cellular mechanisms for recovery from double-strand DNA breaks (DSB) induced by RNA-guided programmable nuclease CRISPR/Cas. Since NHEJ is equivalent to using a duck tape to stick two pieces of metals together, the outcome of this repair mechanism is prone to error. Any out-of-frame mutations or premature stop codons resulting from NHEJ repair mechanism are extremely handy for loss-of-function studies. Substitution of a mutation on the genome with the correct exogenous repair DNA requires coordination via an error-free HDR, for targeted transgenesis. However, several practical limitations exist in harnessing the potential of HDR to replace a faulty mutation for therapeutic purposes in all cell types and more so in somatic cells. In germ cells after the DSB, copying occurs from the homologous chromosome, which increases the chances of incorporation of exogenous DNA with some degree of homology into the genome compared with somatic cells where copying from the identical sister chromatid is always preferred. This review summarizes several strategies that have been implemented to increase the frequency of HDR with a focus on somatic cells. It also highlights the limitations of this technology in gene therapy and suggests specific solutions to circumvent those barriers.

• Journal of Nutrition and Health
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• 제26권3호
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• pp.313-324
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• 1993

Sister chromatid exchange(SCE) has recently become a common cytogenic assay system for detecting exposure to chemical mutagens and carcinogens. One application of SCE is the monitoring of populations believed to be exposed to such agents. A cross-sectional study of SCE frequency in peripheral blood lymphocytes from 40 college students aged 18 to 26 years was conducted. The effects of cigarette smoking alcohol and coffee consumption, dietary and environmental factors on SCE were assessed. A mean spontaneous SCE per cell for the smokers(4.88$\pm$0.17). The SCE levels of the smokers were associated with the personal smoking amount ; the observed increase in the SCE frequency correlated with the number of cigarettes smoked per day (P<0.05). There was no effect of age on SCE. There were positive linear relationship between SCE and food frequency score of meat and fish group (P<0.05) or instant food group(P<0.01) in non-smokers. But in smokers, a significant inverse association between SCE and food frequency score of green and yellow vegetable group(P<0.05). Alcohol intake produced a significant increase(P<0.01) of SCE in comparison with the mean SCE for those not drinking alcohol in combine subjects. Other dietary parameters, including coffee intake, use of artificial sweetners and processed foods, did not show any increase in SCE. SCEs were inversely related to blood glucose and serum cholesterol levels of the combine subjects. No significant correlations were found between SCE frequencise and any other hematological parameters of the subjects.

• 한국환경성돌연변이발암원학회지
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• 제16권2호
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• pp.83-87
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• 1996

This study was performed by the sister chromatid exchanges (SCEs) to investigate the effects of Aphidicolin (APC) or 2, 4-dinitrophenoi (DNP) on cross-adaptive response to ultraviolet radiation (UV) or ethyl methanesulfonate (EMS) in Chinese hamster ovary (CHO) cells. The pretreatment with 1 J/m$^2$ UV decreased the yield of SCEs induced by subsequent treatment with 8 mM EMS in CHO cells. And the treatment with 10 $\mu$g/ml APC or 50 $\mu$M DNP during incubation after pretreatment with 1 J/m$^2$ UV increased the yield of SCEs induced by 8 mM EMS. The pretreatment with 2 mM EMS decreased the yield of SCEs induced by subsequent treatment with 5 J/m$^2$ UV. The treatment with 10 $\mu$g/ml APC during incubation after 2 mM EMS increased the yield of SCEs induced by 5 J/m$^2$ UV. These results suggest that APC and DNP inhibit cross-adaptive response to pretreatment with UV and subsequent treatment with EMS, and also cross-adaptive response to pretreatment with EMS and subsequent treatment with UV is inhibited by APC in CHO cells.

• Journal of Nutrition and Health
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• 제34권4호
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• pp.401-408
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• 2001

The spontaneous frequency of genetic damage and the possible relationship of this damage to total radical-trapping antioxidant potential(TRAP) and antioxidant vitamins, including plasma levels of $\alpha$-carotene, $\beta$-carotene, cryptoxanthin, retinol, $\alpha$-tocopherol and ${\gamma}$-tocopherol in humans were investigated in 57 subjects using two indices of genetic damage, SCE & HFC frequency. The mean of SCE and HFC frequencies were weakly correlated with plasma TRAP(r=-0.305, p<0.1 for SCEs: r=-0.297, p<0.1 for HFCs, respectively), but those were strongly negatively correlated with plasma $\beta$-carotence(r=-0.385, p<0.01 for SCEs : r=-0.392, p<0.01 for HFCs) and cryptoxanthin(r=-0.312, p<0.05 for SCEs : r=0.335, p<0.05 for HFCs, respectively) levels in the subjects. However, those DNA damage markers including SCE and HFC did not correlate with either plasma $\alpha$-carotene, $\alpha$-tocopherol or retinol concentrations. The mean of SCE and HFC frequencies were positively correlated with plasma ${\gamma}$-tocopherol level(r=0.421, p<0.01 for SCEs : r=0.399, p<0.01 for HFCs, respectively). These findings indicate that increased cytogenetic DNA changes, as determined by SCE and HFC frequencies are possibly associated with generation of free radicals in lymphocytes and decreased plasma antioxidant vitamin($\beta$-carotene and cryptoxanthin) status in the subjects. (Korean J Nutrition 34(4) : 401~08, 2001)

• Journal of Nutrition and Health
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• 제36권8호
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• pp.851-858
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• 2003

Sister chromatid exchange (SCE) has recently become a common cytogenic assay system for detecting exposure to chemical mutagens and carcinogens. One application of SCE is the monitoring of populations believed to have been exposed to such agents. A cross-sectional study of SCE frequency in peripheral blood lymphocytes from 45 Koreans aged 61 to 84 years was conducted. The effect of cigarette smoking and age on SCE was assessed by different degrees of smoking status such as smokers (n = 14), ex-smokers (n = 16) and non-smokers (n = 15). Mean spontaneous SCE per cell for the smokers (11.5 $\pm$ 1.1) was significantly higher (p < 0.05) than that for the non-smokers (8.8 $\pm$ 0.3). However, mean SCE frequencies per cell for the ex-smokers (10.3 $\pm$ 0.6) were not significantly different from those of the smokers or the non-smokers. The smokers showed an increased number of high SCE frequency cells (HFCs) when compared to the ex-smokers and non-smokers (p < 0.05). The mean SCE frequencies of the non-smokers showed a statistically significant increase (p < 0.05) with the subject's age. These results show that age and smoking habits contribute a great deal in setting a higher degree of basal DNA damage in elderly Koreans, and smoking appeared to be a more significant damaging factor than age.

• 한국환경성돌연변이발암원학회지
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• 제15권2호
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• pp.94-99
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• 1995

The adaptive response and cross-adaptive response to sister chromatid exchanges (SCEs) and DNA single-strand breaks (SSBs) in Chinese hamster ovary (CHO)-K$_1$ cells treated with ultraviolet radiation (UV), ethyl methanesuffonate (EMS), or bleomycin (BLM) were investigated. Two assays were used in this study; SCEs and alkaline elution. The pretreatment with low conditioning dose of 2 mM EMS or 1 J/m$^2$ UV decreased the yield of SCEs induced by subsequent treatment with 8 mM EMS, 5 J/m$^2$ UV or 5 $\mu$g/ml BLM. And the pretreatment with low conditioning dose of 1 $\mu$g/ml BLM decreased the yield of SCEs induced by subsequent treatment with 5 $\mu$g/ml BLM or 5 J/m$^2$ UV. The rejoining of DNA SSBs in cells subsequently treated with 2 J/m$^2$ UV, 50 mM EMS or 400 $\mu$g/ml BLM is higher than that only treated with 2 J/m$^2$ UV, 50 mM EMS or 400 $\mu$g/ml BLM. These results suggest that there are the adaptive response and cross-adaptive response to SCEs, and is the adaptive response to the rejoining of DNA SSBs in CHO cells.

• Molecules and Cells
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• 제45권11호
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• pp.792-805
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• 2022

Repairing damaged DNA and removing all physical connections between sister chromosomes is important to ensure proper chromosomal segregation by contributing to chromosomal stability. Here, we show that the depletion of non-SMC condensin I complex subunit H (NCAPH) exacerbates chromosome segregation errors and cytokinesis failure owing to sister-chromatid intertwinement, which is distinct from the ultra-fine DNA bridges induced by DNA inter-strand crosslinks (DNA-ICLs). Importantly, we identified an interaction between NCAPH and GEN1 in the chromatin involving binding at the N-terminus of NCAPH. DNA-ICL activation, using ICL-inducing agents, increased the expression and interaction between NCAPH and GEN1 in the soluble nuclear and chromatin, indicating that the NCAPH-GEN1 interaction participates in repairing DNA damage. Moreover, NCAPH stabilizes GEN1 within chromatin at the G2/M-phase and is associated with DNA-ICL-induced damage repair. Therefore, NCAPH resolves DNA-ICL-induced ultra-fine DNA bridges by stabilizing GEN1 and ensures proper chromosome separation and chromosome structural stability.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2487-2490
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• 2013

In Thai traditional medicine, Plumbago indica or Jetamul-Pleung-Dang in Thai is known to have health benefit especially for anti-inflammatory, antibacterial, and antitumor activities. However, the mechanisms of its action are still uncertain. One of which might be genotoxic effects. In the present study, we investigated the genotoxicity of an ethanolic extract of Plumbago indica root (EEPIR) by sister chromatid exchange (SCE) assay in human lymphocytes. Results have shown that all treatments with EEPIR ($12.5-100{\mu}g/ml$) could induce cell cycle delay as shown by significant increase in the number of metaphase cells in the first cell cycle but neither in the second nor the third cell cycle. Only at concentrations of 25, 50, and $100{\mu}g/ml$ were SCE levels significantly increased above that of the control (p<0.05). EEPIR at a concentration of $500{\mu}g/ml$ induced cell death as few mitotic cells were shown. Accordingly, EEPIR ($25-100{\mu}g/ml$) is genotoxic in human lymphocytes and cytotoxic at concentrations of ${\geq}500{\mu}g/ml$ in vitro. Therefore, these activities of the EEPIR could serve its potential therapeutic effects, especially as an anticancer agent. Further study of EEPIR in vivo is now needed to support this in vitro evidence.