• Radiation Oncology Journal
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• 제22권3호
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• pp.208-216
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• 2004

목적: DNA-dependent protein kinase (DNA-PK)는 serine/threonine kinase로 470 kDa의 catalytic subunit (DNA- PKcs) 와 각각 70 kDa과 86 kDa의 무게를 갖는 Ku 70, Ku 80 단백질로 구성된다. 이 DNA-PK는 방사선에 의해 DNA의 두 가닥이 동시에 절단되는 경우 DNA 손상 복구에 핵심적 역할을 하는 것으로 알려져 있다. 본 연구에서 Ku 발현과 이온화방사선에 민감도와의 상관 관계를 알아보고자 하였다. 대상 및 방법: 예비실험으로 두경두종양 기원의 세포주 9개에 대한 방사선에 대한 민감도실험을 한 결과 AMC-HN3이 방사선에 가장 민감하였고, AMC-HN9이 방사선에 가장 저항성을 보여 2개의 세포주에 대한 Ku70/80의 발현을 Western blot과 면역형광 염색을 시행하여 방사선의 반응도와의 상관관계를 알아보았다. 결과: 방사선에 저항성을 보이는 AMC-HN9에서 Ku80 발현이 높았고 방사선에 민감한 AMC-HN3에서 세포자멸사가 더 많이 일어남을 관찰할 수 있었다. 결론: Ku80 단백질 발현이 높은 세포는 방사선에 대한 DNA손상 복구가 많이 되어 방사선에 대한 내성을 보이는 것으로 생각되었다.

• 한국식품영양과학회지
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• 제36권10호
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• pp.1271-1278
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• 2007

미더덕과 오만둥이는 독특한 향과 맛이 있는 식품으로 널리 알려져 있으며 우리나라 전역에서 자생하나 경상남도 마산에서 가장 많이 생산되고 있는 해양생물이다. 한편, 과량의 에탄올 섭취는 microsomal ethanol oxidizing system(MEOS)에 의한 에탄을 산화를 증가시켜 superoxide ion, hydrogen peroxide, hydroxyl radical, 1-hydroxyethyl radical과 같은 활성산소종을 생성하여 산화적 스트레스 상태를 유발하게 된다. 본 연구에서는 미더덕과 오만둥이의 보충투여가 과량의 에탄을 투여로 인해 유도되는 간기능 관련 지표와 간세포 및 백혈구 DNA손상정도에 미치는 영향을 보고자 SD계 수컷 쥐를 세 군으로 나누어 6주간 25% 에탄을 용액을 자유로이 섭취하게 하면서 동결 건조하여 분말화한 미더덕과 오만둥이를 식이의 3%(w/w) 수준으로 보충투여하였다. 6주간의 미더덕과 오만둥이 투여는 체중증가 량, 식이 및 에탄을 섭취량, 간을 비롯한 각종 장기무게에는 아무런 영향을 끼치지 않았다. 미더덕과 오만둥이 보충투여는 총 콜레스테롤을 비롯한 혈장 지질 수준에는 유의적인 영향이 없었지만, 혈장 ALT, ALP, LDH 활성 등 간기능 관련 지표들을 유의적으로 감소시켰다. 또한 미더덕과 오만둥이는 과량의 에탄을 섭취로 유도된 흰쥐의 백혈구, 간세포의 DNA손상을 유의적으로 감소시킨 것으로 나타났으며, 간세포 DNA 손상도는 혈장 ALP와 LDH 활성과 유의적인 양의 상관관계를 보여주었다. 결론적으로 미더덕과 오만둥이 분말의 보충투여는 알코올 섭취로 인해 유도된 간조직 손상에 대한 보호작용이 있는 것으로 사료된다.$ 수준은 GTP 20%를 첨가한 식이를 제공받은 군에서 유의적으로(p<0.05) 감소하였다 간의 TG와 TBARS 수준은 GTP 20%를 첨가한 식이를 제공받은 군에서 감소하는 경향을 보였으며 GTP의 첨가가 간에서의 GSH함량 및 항산화 효소계의 활성을 증진시키는 것으로 나타났다. GTP를 첨가한 식이를 섭취한 실험군의 1일 변중의 총 지방 및 TG 배설량은 유의적인 차이는 보이지 않았으나 OVX-C군에 비해 다소 높은 경향을 보였으며 총 콜레스테롤 배설량은 OVX-C군에 비해 높은 수준이었다. 난소 절제 흰쥐에서 5% GTP를 제공받은 군에 비해 20% GTP를 첨가한 식이를 제공받은 군에서 혈액과 간에서의 지질농도 감소와 항산화 효소의 활성이 높은 수준을 보여 GTP의 첨가량이 높을수록 더 효과적인 것으로 나타났다. 이상의 결과들로 미루어 볼 때 난소절제 흰쥐에서 GTP 첨가가 변의 총지질과 TG및 콜레스테롤 배설을 증가시켜 혈청과 간의 총 지질 농도와 TG및 총콜레스테롤 농도를 감소시키는 것과 관련이 있는 것으로 보이며 GTP의 섭취가 체내 총 지질 농도를 감소시켜 항 동맥경화 작용을 나타내는 것으로 사료된다. 따라서 녹차가공품의 폐경기 고지혈증 개선을 위한 기능성식품으로의 가능성을 보여 준다고 할 수 있다.용적중 등 품질 평가 기준에서 차이가 없었다.50 에서는 43% 발효주에는 0.95 cm, 45% 고은 발효주에는 0.95 cm의 항균성을 나타냈으며 관능평가에서도 가장 높게 났다. 관능평가에서는 45% 고온 발효주가 가장 높게 나타났으며, 항산화성 실험에 나타난 저온 45%의 갈색도의 측정과는 항산화성에서는 좀 다른 결과를 나타낸다. 그러나 항균성이 가장

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6121-6128
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• 2012

Radiation-induced side effects on normal tissue are determined largely by the capacity of cells to repair radiation-induced DNA damage. X-ray repair cross-complementing group 1 (XRCC1) plays an important role in the repair of DNA single-strand breaks. Studies have shown conflicting results regarding the association between XRCC1 gene polymorphisms (Arg399Gln, Arg194Trp, -77T>C and Arg280His) and radiation-induced side effects in patients undergoing whole breast radiotherapy. Therefore, we conducted a meta-analysis to determine the predictive value of XRCC1 gene polymorphisms in this regard. Analysis of the 11 eligible studies comprising 2,199 cases showed that carriers of the XRCC1 399 Gln allele had a higher risk of radiation-induced toxicity than those with the 399 ArgArg genotype in studies based on high-quality genotyping methods [Gln vs. ArgArg: OR, 1.85; 95% CI, 1.20-2.86] or in studies with mixed treatment regimens of radiotherapy alone and in combination with chemotherapy [Gln vs. ArgArg: OR, 1.60; 95% CI, 1.09-2.23]. The XRCC1 Arg399Gln variant allele was associated with mixed acute and late adverse reactions when studies on late toxicity only were excluded [Gln allele vs. Arg allele: OR, 1.22; 95% CI, 1.00-1.49]. In contrast, the XRCC1 Arg280His variant allele was protective against radiation-induced toxicity in studies including patients treated by radiotherapy alone [His allele vs. Arg allele: OR, 0.58; 95% CI, 0.35-0.96]. Our results suggest that XRCC1 399Gln and XRCC1 280Arg may be independent predictors of radiation-induced toxicity in post-surgical breast cancer patients, and the selection of genotyping method is an important factor in determining risk factors. No evidence for any predictive value of XRCC1 Arg194Trp and XRCC1 -77T>C was found. So, larger and well-designed studies might be required to further evaluate the predictive value of XRCC1 gene variation on radiation-induced side effects in patients undergoing whole breast radiotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1773-1777
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• 2016

Diagnostic and therapeutic radiation fields are planned so as to reduce side-effects while maximising the dose to site but effects on healthy tissues are inevitable. Radiation causes strand breaks in DNA of exposed cells which can lead to chromosomal aberrations and cause malfunction and cell death. Several researchers have highlighted the damaging effects of high dose radiation but still there is a lacuna in identifying damage due to low dose radiation used for diagnostic purposes. Blood is an easy resource to study genotoxicity and to estimate the effects of radiation. The micronucleus assay and chromosomal aberration can indicate genetic damage and our present aim was to establish these with lymphocytes in an in vitro model to predict the immediate effects low dose radiation. Blood was collected from healthy individuals and divided into 6 groups with increasing radiation dose i.e., 0Gy, 0.10Gy, 0.25Gy, 0.50Gy, 1Gy and 2Gy. The samples were irradiated in duplicates using a LINAC in the radiation oncology department. Standard protocols were applied for chromosomal aberration and micronucleus assays. Metaphases were stained in Giemsa and 200 were scored per sample for the detection of dicentric or acentric forms. For micronuclei detection, 200 metaphases. Giemsa stained binucleate cells per sample were analysed for any abnormality. The micronuclei (MN) frequency was increased in cells exposed to the entire range of doses (0.1-2Gy) delivered. Controls showed minimal MN formation ($2.0%{\pm}0.05$) with triple MN ($5.6%{\pm}2.0$) frequency at the lowest dose. MN formation increased exponentially with the radiation dose thereafter with a maximum at 2Gy. Significantly elevated numbers of dicentric chromosomes were also observed, even at doses of 0.1-0.5Gy, compared to controls, and acentric chromosomes were apparent at 2Gy. In conclusion we can state that lymphocytes can be effectively used to study direct effect of low dose radiation.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3637-3643
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• 2012

Objective: Non-homologous end joining (NHEJ) is a pathway for repairing DNA double-strand breaks. Recent publications indicated that XRCC5, XRCC6 and XRCC7 genes may participate in the pathogenesis of breast cancer. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate associations between XRCC5, XRCC6 and XRCC7 genetic polymorphisms in the NHEJ pathway and breast cancer risk. Methods: Studies focusing on the relationship between genetic polymorphisms in XRCC5, XRCC6 and XRCC7 genes and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers. The meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. The odds ratio (OR) with 95% confidence interval (95%CI) was calculated based on the extracted data. Results: According to the inclusion criteria, we final included seven studies with a total of 2,864 breast cancer cases and 3,060 healthy controls. Meta-analysis results showed that rs3835 (G>A) and rs828907 (G>T) in XRCC5 gene, and rs132793 (G>A) in XRCC6 gene might increase the risk of breast cancer, while rs132788 G>T and rs6002421 (A>G) might be protective factors. However, there was no relationship between XRCC7 genetic polymorphisms and the risk of breast cancer. Conclusion: This meta-analysis suggests that the rs3835 G>A and rs828907 G>T in XRCC5 gene, rs6002421 (A>G), rs132788 (G>T) and rs132793 (G>A) in XRCC6 gene might be risk factors for breast cancer, while the rs132788 (G>T) and rs6002421 (A>G) in XRCC6 gene might be protective.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10675-10681
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• 2015

Background: The ataxia telangiectasia mutated (ATM) protein and p53 play key roles in sensing and repairing radiation-induced DNA double strand breaks (DSBs). Accumulating epidemiological evidence indicates that functional genetic variants in ATM and TP53 genes may have an impact on the risk of radiotherapy-induced side effects. Here we performed a meta-analysis to investigate the potential interaction between ATM Asp1853Asn and TP53 polymorphisms and risk of radiotherapy-induced adverse effects quantitatively. Materials and Methods: Relevant articles were retrieved from PubMed, ISI Web of Science and the China National Knowledge Infrastructure (CNKI) databases. Eligible studies were selected according to specific inclusion and exclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled to estimate the association between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and risk of radiotherapy adverse effects. All analyses were performed using the Stata software. Results: A total of twenty articles were included in the present analysis. In the overall analysis, no significant associations between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and the risk of radiotherapy adverse effects were found. We conducted subgroup analysis stratified by type of cancer, region and time of appearance of side effects subsequently. No significant association between ATM Asp1853Asn and risk of radiotherapy adverse effects was found in any subgroup analysis. For TP53 Arg72Pro, variant C allele was associated with decreased radiotherapy adverse effects risk among Asian cancer patients in the stratified analysis by region (OR=0.71, 95%CI: 0.54-0.93, p=0.012). No significant results were found in the subgroup analysis of tumor type and time of appearance of side effects. Conclusions: The TP53 Arg72Pro C allele might be a protective factor of radiotherapy-induced adverse effects among cancer patients from Asia. Further studies that take into consideration treatment-related factors and patient lifestyle including environmental exposures are warranted.

• Archives of Pharmacal Research
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• 제18권6호
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• pp.410-414
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• 1995

Adaptive response induced by low dese .gamma.-ray irradiation in human cervical carcinoma cells was examined. Cells were exposured to low dose of .gamma.-ray irradiation in human cervical carcinoma cells was examined. Cells were exposured to low dose of .gamma.-ray (1-cGy) followed by high doses of r-ray irradiation (0,1,2,3,5,7 and 9Gy for chlnogenic assay or 1.5Gy for micronucleus assay) with various time intervals. Survival fractions of cells in both low dose-irradiated and unirrated groups were analyzed by clonogenic assay. Surviva fractions of low dose-irradiated in cell survival was maximum when low and high dose irradiation time interval was 4 hr. Frequencies of micronuclei which is an indicative of chromosome aberration were also enutained from survival fractions analyzed by clonogenic assay, maximum when low and high dose irradiation time interval was 4hr. Frequencies of micronuclei which is an indicative of chromosome aberration were also enumerated in both low dose-irradiated and unirradiated groups. In consiststent with the result obtained from survival fractions analyzed by clonogenic assay, maximum reduction in frquencies of micronuclei was observed when low dose radiation was given 4 hr prior to high response to subsequent high dose .gamma.-ray irradiation in human cervical carcinomal cells. Our data suggest that one of the possible mechanisms of adaptive response induced by low dose rediation is the increase in repair of DNA double strand breaks in low dose radiation-adapted cells.