• Nuclear Engineering and Technology
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• 제38권3호
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• pp.285-292
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• 2006

Thermoresistant (TR) clones of radiation-induced fibrosarcoma (RIF) cells have been reported to show an adaptive response to 1cGy of low dose radiation, and HSP25 and inducible HSP70 are involved in this process. In this study, to further elucidate the mechanism by which HSP25 and inducible HSP70 regulate the adaptive response, HSP25 or inducible HSP70 overexpressed RIF cells were irradiated with 1cGy and the cell cycle was analyzed. HSP25 or inducible HSP70 overexpressed cells together with TR cells showed increased G1 phase after 1cGy irradiation, while RIF cells did not. $[^3H]-Thymidine$ and BrdU incorporation also indicated that both HSP25 and inducible HSP70 are involved in G1 arrest after 1cGy irradiation. Molecular analysis revealed upregulation of p27Cip/Kip protein in HSP25 and inducible HSP70 overexpressed cells, and cotransfection of p27Cip/Kip antisense abolished the induction of the adaptive response and 1cGy-mediated G1 arrest. The above results indicate that induction of an adaptive response by HSP25 and inducible HSP70 is mediated by upregulation of p27Cip/Kip protein, resulting in low dose radiation-induced G1 arrest.

• Journal of Radiation Protection and Research
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• 제20권2호
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• pp.97-102
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• 1995

인체 말초 혈액 림프구에서 저선량의 감마선에 의해 유도되는 적응 반응을 관찰하였다. 인체 림프구를 저선량의 감마선(priming dose 0.01Gy) 을 조사한 후 여러 시간 간격 후 고선량 (challenging dose, 1.5Gy) 을 조사하였다. 저선량을 미리 조사한 림프구와 조사하지 않은 림프구에서 발생된 미세핵의 빈도를 계수하였다. 비세핵 발생 빈도는 저선량 조사 4시간 후 고선량을 조사하였을 때 최대 감소치를 보였다. 저선량과 고선량 조사 시간차가 7시간 또는 20시간이었을 때 미세핵 발생 빈도는 약간 감소하였으나 유의성은 없었다. 본 연구에서는 $G_0$상태의 세포주기에서 저선량을 조사하였을 경우 적응 반응이 나타나는 것이 관찰 되었다. 미세핵 분석법은 실험 방법이 비교적 간단하고, 기타 염색체 분석법에 비하여 빠른 시간내 결과를 도출 할 수 있어 추후 방사선에 대한 적응 반응의 연구에 유용한 지표가 될 수 있을 것이다.

• 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.

• Archives of Pharmacal Research
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• 제20권3호
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• pp.212-217
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• 1997

Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of ${\gamma}$-rays (0.01 Gy) 4 or 20 hrs prior to high dose ${\gamma}$-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose .gamma.-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-.betha.-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose ${\gamma}$-ray irradiation to high dose ${\gamma}$-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis.

• 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.

• Radiation Oncology Journal
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• 제17권4호
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• pp.307-313
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• 1999

목적 : 방사선에 의한 apoptosis 유도에 저선량 방사선이 미치는 영향을 관찰하여 adaptive response 현상이 관계되는지를 마우스 종양에서 분석하고 관련되는 기전에 관하여 연구하고자 하였다. 대상 및 방법 : 마우스 동종암인 HCa-I, OCa-I에서 저선량 (0.05 Gy) 방사선 조사 후 고선량 (25 Gy)을 조사하여 이로부터 일정시간 후 종양에서 유도된 apoptosis 수준을 비교분석하였다. 또한, apoptosis의 조절 물질인 p53, Bcl-2, Bax, Bcl-X 등의 발현을 Western blotting으로 분석하여 관련된 기전을 연구하였다. 결과 : OCa-l에서 0.05 Gy를 전처치 후에 25 Gy를 조사한 군에서 apoptosis의 유도 수준은 세포 1000개당 229로서 예상되는 값인 324 에 비하면 약 $30\%$정도 감소된 결과로 나타나서(p<0.05) 저선량의 방사선에 의하여 apoptosis의 유도 수준이 감소한 것으로 나타났다. 반면 HCa-l기에서는 예상된 apoptosis수준과 실제 관찰치간에 변화가 없었다. 유전물질의 발현에서 p53은 두 종양 공히 0.05 Gy 조사군, 25 Gy 조사군 및 0.05+25 Gy 조사군에서 발현이 증가되었다. Bcl-2와 Bax는 두 종양 모두 발현 수준의 등락이 현저하지는 않았으나 OCa-l의 0.05+25 Gy 조사군에서 Bcl-2의 발현이 Bax를 상회하는 결과를 보였다. Bcl-X는 HCa-l에서 0.05 Gy 정도의 저선량에서부터 높은 상승을 보인 반면, OCa-l기에서는 천혀 발현되지 않았다. 결론 : 마우스 종양의 일부에서 0.05 Gy의 저선량이 고선량 방사선에 의한 apoptosis 유도에 대하여 adaptive response를 보이는 것으로 나타났다. 이는 Bcl-2, Bax의 발현 수준과 BcI-X 등이 관련되는 것으로 보였다. 본 연구는 방사선에 의한 apoptosis에서 adaptive response의 관련성이 일정치 않다는 것을 마우스 종양에서 보여주었다.

• 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.

• 한국방사성폐기물학회:학술대회논문집
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• 한국방사성폐기물학회 2004년도 학술대회지
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• pp.210.1-210.1
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• 2004

• Animal cells and systems
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• 제5권1호
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• pp.77-83
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• 2001

The present study was conducted to elucidate whether the expression level of poly(ADP-ribose) polymerase (PARP) is related to the ultraviolet radiation (UV)-induced apoptosis. After treatment of the mammalian cell lines HeLa S3 and Chinese hamster ovary (CHO) with 50 J/m2 UV, induction of apoptosis was determined by several means during 24 h post-incubation. Incidence of apoptosis was much lower in CHO than HeLa S3 cells based on the percentage of apoptotic cells in terms of morphological changes in nucleus or direct counting of viable cells and qualitative or quantitative DNA fragmentation. Interestingly, when the expression level of PARP was measured by western blotting, the amounts of PARP that was retained at each time point inversely correlated with the incidences of apoptosis in these cells. Concomitant with generation of the 85 kDa fragment, 116 kDa PARP disappeared in HeLa S3 within 6 h after UV treatment, whereas a fair amounts of 116 kDa band was still retained in CHO cells at 36 h post-incubation. This inverse relationship was also observed in the adaptive response system, in which cells weve treated with a high dose of UV after pretreatment with a low dose. As expected, typical adaptive responses appeared in CHO cells but not in HeLa cells, showing greater cell viability and lesser DNA fragmentation. During the adaptive response in CHO cells, PARP was expressed at much higher level compared to the single, high dose-treated cells. Interestingly, even though PARP was induced at 6 h post-incubation In both cell types, its expression was more prominent in CHO cells. Thus, our data indicate that the retained level of intact PARP against UV damage inversely correlates with incidence of apoptosis in mammalian cells, and also suggest that a machinery to protect the PARP degradation against UV damage exists in CHO but not in HeLa S3 cells.

• 환경생물
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• 제22권3호
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• pp.472-477
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• 2004

본 연구에서는 감마선으로 유도된 돌연변이체들에서 공통으로 발현되는 방사선 관련 유전자들의 발현을 연구하기 위하여, B. lentimorbus WJ5 의 방사선 유도 돌연변이체에서 발현되는 유전자를 DNA microarray로 동시에 탐색하였다. DNA microarray는 B. lentimorbus WJ5 genome을 무작위로 절단하여 2,000 단편으로 구성하였으며, 감마선 $(^{60}/Co)$으로 유도된 7 돌연변이체의 발현을 정량적으로 관찰하였다. 클러스터 분석결과 발현된 408 유전자 중 27개가 감마선 유도 돌연변이체 모두에서 유의하게 발현이 증가되었다. 특히, 복구(mutL, mutM) 에너지 대사 (acsA, sdhB, pgk, yhjB, citB), protease (npr), 산화자극에 대한 환원 (HMM)관련 유전자들이 동시에 증가되었다. 이는 감마선 유도 돌연변이체들에서 자발적인 직/간접 복구 관련 유전자의 발현 증가는 방사선 노출 직후 보이는 stress response와는 다른 현상임을 나타내는 것으로 생각된다.