• Radiation Oncology Journal
• /
• 제23권3호
• /
• pp.161-168
• /
• 2005

목적: 강력한 항산화 효과를 지닌 melatonin을 전처치하였을 때 방사선유도성 섬유증 과정에서 중요한 사이토카인인 $TGF-{\beta}1$의 변화된 발현양상을 마우스 폐에서 연구하였다. 대상 및 방법: C57BL/6 마우스를 실험군에 따라 세 군(대조군, 방사선조사 단독군, melatonin 전처치군(방사선조사 1시간 전에 300 mg/kg 복강주사))으로 분류하고 양측 흉곽에 12 Gy의 선량을 단일조사하였다. 방사선조사 후 2주와 4주의 폐조직에서 $TGF-{\beta}1$ mRNA 발현수준을 측정하기 위해 semiquantitive RT-PCR를 시행하였고, $TGF-{\beta}1$ protein 발현의 수준과 위치를 보기 위해 면역조직화학염색을 시행하였다. 결과: 2주 후에 측정된 mRNA 발현은 방사선조사 단독군과 melatonin 전처치군에서 각각 대조군의 1.92배와 1.80배 증가된 수준을 보였고(p=0.064), 4주 후에는 각각 2.38배와 1.94배 수준의 증가된 발현을 보였다(p=0.004). $TGF-{\beta}1$ protein의 발현은 조직병리학적으로 방사선손상 영역에서 주로 관찰되었는데 폐포 대식세포와 폐포벽의 상피세포들이 주요 근원이었다. 발현수준은 2주완 4주 후에 각각 $15.8\%\;vs\;16.9\%$ (P=0.565), 그리고 $36.1\%\;vs\;25.7\%$ (p=0.009)이었다. 결론: Melatonin 전처치로 방사선조사에 의한 $TGF-{\beta}1$ mRNA와 protein의 발현이 4주 후에 유의하게 감소됨을 관찰하였다. 따라서 방사선으로 인한 폐손상 시에 항섬유증 약물로의 사용가능성을 확인하였다.

• Radiation Oncology Journal
• /
• 제28권1호
• /
• pp.32-38
• /
• 2010

목 적: 항암요법에 의한 부작용 중 방사선섬유증(radiation fibrosis)은 방사선치료 후 빈번하게 일어나지만 발생빈도 및 심각성에 비해 치료법이 제한적이다. 본 연구에서는 방사선섬유증의 기전 연구 및 치료제 개발을 위해 방사선섬유증 동물모델계를 확립하고자 하였다. 대상 및 방법: 마우스의 대퇴부에 20 Gy의 방사선을 1주 간격으로 2회 조사한 후 날짜 별로 육안적 평가와 haematoxylin & eosin (H&E) 및 Masson’s Trichrome 염색을 통한 조직학적 변화를 평가하였다. 연부조직 수축도를 평가하기 위하여 특별히 고안된 틀을 이용하여 양쪽 하지의 길이 차이를 측정하였고, transforming growth factor (TGF)-${\beta}$의 발현 정도를 면역조직염색 및 중합효소연쇄반응(polymerase chain reaction)을 통해 측정하였다. 결 과: 본 연구에서 20 Gy씩 2회의 방사선조사를 시행하고 14, 28, 42, 97일 후 양측 하지의 수축도를 비교한 결과 42일 이후에 유의한 길이 차이가 나타났고 조직검사 결과 방사선이 조사된 피부 및 연부조직에서 아교질(collagen)과 세포외바탕질(extracellular matrix) 섬유가 불규칙한 배열을 나타내었으며 근육섬유모세포(myofibroblast)의 증가가 관찰되었다. TGF-${\beta}$ 발현 정도를 면역염색으로 조사한 결과 시간이 지남에 따라 증가하였고, 중합효소연쇄반응상 mRNA 발현량도 대조군에 비해 유의하게 증가하였다. 결 론: BALB/c 마우스의 대퇴부에 20 Gy의 방사선을 2회 조사하였을 때 방사선섬유증과 관련된 주요 인자인 TGF-${\beta}$의 발현량이 증가하였을 뿐만 아니라 외관적으로도 뚜렷한 방사선섬유증이 관찰되어 앞으로의 연구를 위한 효과적인 동물모델계로 사료된다.

• Journal of Radiation Protection and Research
• /
• 제36권3호
• /
• pp.119-126
• /
• 2011

Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging, and contributes to harmful effects in cultured cells and animal tissues. mtDNA biogenesis genes (NRF-1, TFAM) are essential for the maintenance of mtDNA, as well as the transcription and replication of mitochondrial genomes. Considering that oxidative stress is known to affect mitochondrial biogenesis, we hypothesized that ionizing radiation (IR)-induced reactive oxygen species (ROS) causes mtDNA deletion by modulating the mitochondrial biogenesis, thereby leading to cellular senescence. Therefore, we examined the effects of IR on ROS levels, cellular senescence, mitochondrial biogenesis, and mtDNA deletion in IMR-90 human lung fibroblast cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated at 4 or 8 Gy. Old cells at PD55, and H2O2-treated young cells at PD 39, were compared as a positive control. The IR increased the intracellular ROS level, senescence-associated ${\beta}$-galactosidase (SA-${\beta}$-gal) activity, and mtDNA common deletion (4977 bp), and it decreased the mRNA expression of NRF-1 and TFAM in IMR-90 cells. Similar results were also observed in old cells (PD 55) and $H_2O_2$-treated young cells. To confirm that a increase in ROS level is essential for mtDNA deletion and changes of mitochondrial biogenesis in irradiated cells, the effects of N-acetylcysteine (NAC) were examined. In irradiated and $H_2O_2$-treated cells, 5 mM NAC significantly attenuated the increases of ROS, mtDNA deletion, and SA-${\beta}$-gal activity, and recovered from decreased expressions of NRF-1 and TFAM mRNA. These results suggest that ROS is a key cause of IR-induced mtDNA deletion, and the suppression of the mitochondrial biogenesis gene may mediate this process.

• 대한방사선기술학회지:방사선기술과학
• /
• 제41권6호
• /
• pp.581-586
• /
• 2018

This study was conducted to analyze factors Influencing Protective Behavior against Radiation Exposure using questionnaires for 231 radiological technologists working in Computed Tomography(CT) examination room with high radiation dose in diagnostic radiology field. Statistical analysis of the collected data revealed that the reasons for partially shielding the examination part in the CT scan were the lack of protective equipment, securing of radiation justification, being annoying and maybe not being harm to adults in order. It was also revealed that the variables influencing the protective behavior were protective behavior against radiation harm, self-efficacy, protective environment, organization culture, protective knowledge and protective instrument in order. The higher the radiological protective environment(${\beta}=0.245$) and the lower the radiological protective knowledge(${\beta}=-0.034$), the more influential the protective behavior against radiation harm was. In this study, it was shown that non examination parts were not shielded in the CT scan. Therefore, it is necessary to improve the level of protective environment, to cultivate knowledge to improve the protective behavior against radiation harm and to have an intervention strategy for concrete action.

• Animal cells and systems
• /
• 제5권4호
• /
• pp.267-274
• /
• 2001

Calpains are a family of cysteine proteases existing primarily in two forms designated by the $Ca^{2+}$ concentration needed for activation in vitro, $\mu$-calpain (calpain-I) and m-calpain (calpain-II). The physiologica1 roles of calpains remain unclear. Many groups have proposed a role for calpains In apoptosis, but their patterns of activation are not well characterized. Calpains have been implicated in neutrophil apoptosis, glucocorticoid-induced thymocyte apoptosis, as well as many other apoptotic pathways. Calpain activation in apoptosis is usually linked upstream or downstream to caspase activation, or in a parallel pathway alongside caspase activation. Calpains have been suggested to be involved in DNA fragmentation (via endonuclease activation), but also as effector proteases that cleave cellular proteins involved in DNA repair, membrane associated proteins and other homeostatic regulatory proteins. Recently, our laboratory demonstrated $\mu$-calpain activation in NAD(P)H: quinone oxidoreducatse 1 (NQO1)-expressing cells after exposure to $\beta$-lapachone, a novel quinone and potential chemo- and radio-therapeutic agent. Increased cytosolic $Ca^{2+}$ in NQO1-expressing cells after $\beta$-lapachone exposures were shown to lead to $\mu$-calpain activation. In turn, $\mu$-calpain activation was important for substrate proteolysis and DNA fragmentation associated with apoptosis. Upon activation, $\mu$-calpain translocated to the nucleus where it could proteolytically cleave PARP and p53. We provided evidence that $\beta$-lapachone-induced, $\mu$-calpain stimulated, apoptosis did not involve any of the known caspases; known apoptotic caspases were not activated after $\beta$-lapachone treatment of NQO1-expressing cells, nor did caspase inhibitors have any effect on $\beta$-1apachone-induced cell death. Elucidation of processes by which $\beta$-1apachone-stimulated $\mu$-calpain activation and calpains ability to activate endonucleases and induce apoptosis independent of caspase activity will be needed to further develop/modulate $\beta$-lapachone for treatment of human cancers that over-express NQO1.

• 한국의학물리학회지:의학물리
• /
• 제21권3호
• /
• pp.281-290
• /
• 2010

최근 디지털 단층영상합성법을 영상유도 방사선 치료에 활용하기 위한 연구가 활발히 시도되고 있다. 적은 수의 투사영상으로 삼차원 영상재구성이 가능하기 때문에 환자에 대한 피폭선량을 줄일 수 있으며, 환자의 움직임을 최소화할 수 있는 장점이 있기 때문이다. 그러나 단층영상의 화질이 스캔 각도(${\beta}_{scan}$) 및 사용한 투사영상의 수 등 촬영조건에 크게 의존하는 단점이 있다. 본 연구에서는 필터링 후 역투사법을 이용한 디지털 단층영상합성의 구현에 대해 자세히 논하였으며, 이에 대한 최적 촬영조건에 대해 살펴 보았다. 이를 위해 시스템 성능을 신호 대 잡음비, 잔상퍼짐함수, 연산횟수를 조합한 이득함수로 정의하였으며, 다양한 촬영조건에 대해 실험을 통해 각 지표를 구한 후 평가하였다. 평가 결과 및 분석으로부터 큰 단위 스캔 각도(${\Delta}{\beta}$)로 60도 이상의 넓은 범위에 걸쳐 스캔을 할수록 높은 화질의 단층영상을 얻을 수 있다는 결론을 얻었다. 대략적으로 시스템 성능이 $\sqrt{{\Delta}{\beta}}{\times}{\beta}^{2.5}_{scan}$에 비례하였다. 만약 각 평가지표에 명확한 가중치를 부여할 수 있다면 보다 엄밀하고 구체적인 촬영조건을 구할 수 있을 것이다.

• Journal of Radiation Protection and Research
• /
• 제24권1호
• /
• pp.39-43
• /
• 1999

최근 개발된 감도가 좋은 LiF:Mg,Cu,Na,Si TL물결을 Teflon과 혼합한 후, 않은 디스크 형태로 압축 성형한 얇은 LiF:Mg,Cu,Na,Si Teflon 검출기를 제작하고 베타선 검출기로서의 TL 반응특성을 연구하였다. 한국원자력연구소의 $^{147}Pm,\;^{204}Tl$ 및 $^{90}Sr/^{90}Y$ 베타선원을 이용하여 두께 $2mg/cm^2$인 Kapton 박막을 덮은 상태로 베타선을 조사하였다. 제작한 않은 LiF:Mg,Cu,Na,Si 검출기들의 $^{137}Cs$에 대한 batch 균질성은 4.7%, 베타선에 대한 선량의존성은 0.1 mGy에서 100 Gy까지 선형성을 나타내고, 에너지의존성은 $^{147}Pm,\;^{204}Tl$ 및 $^{90}Sr/^{90}Y$ 베타선에 대해 각각 0.46, 1.09 및 1.06 이었다. 그리고 베타선에 대한 방향의존성은 $0.93{\pm}0.03\;(^{147}Pm),\;0.94{\pm}0.04\;(^{204}Tl)$ 및 $0.92{\pm}0.05\;(^{90}Sr/^{90}Y)$으로, 이들 얇은 LiF:Mg,Cu,Na,Si 검출기들에 대한 TL 반응특성의 결과는 국제표준기구(ISO)의 베타선량계 기준을 잘 만족하였다.

• 한국식품영양학회지
• /
• 제22권3호
• /
• pp.357-366
• /
• 2009

The principal objective of this study was to evaluate the association between plasma antioxidant levels and metabolic syndrome in male workers, and to provide basic information regarding the control and prevention of metabolic syndrome. We analyzed 163 male workers who had participated in annual medical examinations from January to December 2007. The subjects were classified into normal and metabolic syndrome groups according to the NCEP-ATP III criteria and the Asia-Pacific criteria for waist circumference. Anthropometric parameters, lifestyles, blood lipid profiles, and antioxidant levels were evaluated. As compared to the normal group, the metabolic syndrome group evidenced significantly higher plasma levels of $\alpha$- tocopherol(p<0.05) and retinol(p<0.05), but significantly lower plasma levels of lycopene(p<0.05) and $\beta$-carotene(p<0.05). This tendency was found to be predominantly attributable to increases in the number of metabolic syndrome components. In our simple regression analysis, higher plasma levels of $\alpha$-tocopherol($\beta$=0.001, p<0.01) and retinol($\beta$=0.021, p<0.001) were associated with significantly higher risks of metabolic syndrome, but lycopene($\beta$=-1.499, p<0.01) and $\beta$-carotene($\beta$=-0.048, p<0.01) were associated with significantly lower risks of metabolic syndrome. Retinol($\beta$=0.013, p<0.05) and $\beta$-carotene($beta$=-0.044, p<0.01) were associated significantly with metabolic syndrome, when adjusted for age and BMI. These data indicate that the plasma levels of $\alpha$-tocopherol, retinol, lycopene, and $\beta$-carotene are associated with metabolic syndrome. Specifically, low lycopene and $\beta$-carotene levels in the plasma appear to increase the risk of metabolic syndrome. Therefore, proper nutritional education programs for male workers are required to increase dietary intakes of antioxidant vitamins. Further studies will be necessary to determine whether antioxidant levels can be utilized as a predictive or a preventive factor.

• 한국의학물리학회지:의학물리
• /
• 제23권4호
• /
• pp.285-291
• /
• 2012

Si(Li) 검출기를 이용해 한국표준과학연구원에서 보유한 베타선 선원인 $^{147}Pm$, $^{85}Kr$, $^{90}Sr+^{90}Y$ 선원의 순수 베타선 에너지 스펙트럼을 측정하였고 이 측정 스펙트럼에 대한 잔여에너지와 질량충돌저지능비를 산출하였다. 베타선의 잔여에너지는 $^{147}Pm$, $^{85}Kr$, $^{90}Sr+^{90}Y$ 선원에 대하여 각각 0.14, 0.57, 0.93 MeV으로 평가되었고 질량충돌저지능비는 각각 1.123, 1.120, 1.109이었다.

• Molecules and Cells
• /
• 제25권1호
• /
• pp.105-111
• /
• 2008

Radiotherapy is an important treatment for many malignant tumors, but there are recent reports that radiation may increase the malignancy of cancer cells by stimulating expression of type IV collagenases. In this study, we examined changes in matrix metalloproteinase (MMP) inhibitors, such as the tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2 and RECK, in response to irradiation in Panc-1 pancreatic cancer cells. Irradiation increased RECK protein levels but not mRNA levels, whereas no significant changes were found in TIMP-1 and TIMP-2. The enhanced RECK protein levels were associated with an increase in MMP inhibitory activity. However, irradiation slightly but reproducibly increased the invasiveness of the Panc-1 cells. Like irradiation, treatment of Panc-1 cells with transforming growth factor $(TGF)-{\beta}1$ led to a 2-fold increase in RECK protein levels. Transient transfection with Smad3 also increased RECK protein levels, but transfection with Smad7 markedly reduced them. Stable expression of Smad7 and treatment with SB431542, an inhibitor of $TGF-{\beta}$ receptor I kinase, abolished $TGF-{\beta}1$- and radiation-mediated effects on RECK. Furthermore, irradiation increased levels of phosphorylated Smad3. We conclude that radiation post-transciptionally enhances RECK protein levels in Panc-1 cells, at least in part, via $TGF-{\beta}$ signaling, and that irradiation increases Panc-1 invasiveness via a mechanism that may not be linked to MMP-2 activity.