• Title/Summary/Keyword: dose-response relationship

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Human Dermal Risk Assessment on Chlorpyrifos of Korean Farmers (우리나라 농민의 Chlorpyrifos에 대한 피부 위해성 평가)

  • 정경미;이효민;이은희;이선희;김진화;심영용;홍진태;이용욱
    • Environmental Mutagens and Carcinogens
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    • v.22 no.3
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    • pp.187-198
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    • 2002
  • Chlorpyrifos is an organophosphate insecticide and one of the most commonly and widely used insecticide. However, a little known about the dermal risk of chlorpyrifos on human being. Therefore, this study was conducted for the dermal risk assessment after exposure to chlorpyrifos in Korean farmers. First, skin irritation by chlorpyrifos (10 mg/$\textrm{cm}^2$, 50 mg/$\textrm{cm}^2$, 100 mg/$\textrm{cm}^2$, 250 mg/$\textrm{cm}^2$ in acetone) was determined in rabbits for 5 days considering the usage of chlorpyrifos short term highly exposure. The index of skin irritation by chlorpyrifos was increased in each dose and length of exposure dependent manners. Next, using benchmark dose (BMD$_{5}$) approach, the dose-response relationship was assessed to calculate the reference dose (RfD). The value of RfD was 2.84 $\mu\textrm{g}$/kg/day from 142.16 $\mu\textrm{g}$/kg/day BMD5 value divided uncertainty factor 50. Finally, we assessed human dermal risk of chlorpyrifos with exposure level and RfD. Skin absorbed levels were assumed with several exposure scenarios encounting the circumstances of exposure that application method, protection equipment and cloth, exposure time and exposure frequency during chlorpyrifos spraying. By the comparison of skin absorbed dose with the reference dose, it was identified that risk values (risk index) to skin chlorpyrifos exposure were 0.958 from the point of above results and it was recommended that the occurrence of hazard effect (skin irritation toxicity) of chlorpyrifos would not be expected. Risk index was smaller than 1 in the case of spraying vehicle mounted application, 1hour exposure time and wearing protective cloth exposure. Whereas, risk index was above 1 in the case of hand-held application, 2hour exposure time and wearing common cloth. Comparing two kinds of application method, total risk index of the hand held application (1.67) was higher than vehicle mounted (0.27). Therefore, chlorpyrifos skin exposure was mainly affected by application equipment and applied form. The results of risk assessment on the human dermal toxicity of chlorpyrifos should be required to control in keeping safety rules, skin surface area available for contact, spraying time ,and spraying frequency.y.

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Tobacco Smoke Exposure and Breast Cancer Risk in Thai Urban Females

  • Pimhanam, Chaisak;Sangrajrang, Suleeporn;Ekpanyaskul, Chatchai
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7407-7411
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    • 2014
  • The incidence of urban female breast cancer has been continuously increasing over the past decade with unknown etiology. One hypothesis for this increase is carcinogen exposure from tobacco. Therefore, the objective of this study was to investigate the risk of urban female breast cancer from tobacco smoke exposure. The matched case control study was conducted among Thai females, aged 17-76 years and living in Bangkok or its surrounding areas. A total of 444 pairs of cases and controls were recruited from the Thai National Cancer Institute. Cases were newly diagnosed and histologically confirmed as breast cancer while controls were selected from healthy women who visited a patient, matched by age ${\pm}5$ years. After obtaining informed consent, tobacco smoke exposure data and information on other potential risk factors were collected by interview. The analysis was performed by conditional logistic regression, and presented with odds ratio (ORs) and 95% confidence intervals(CI). From all subjects, 3.8% of cases and 3.4% of controls were active smokers while 11.0% of cases and 6.1% of controls were passive smokers. The highest to lowest sources of passive tobacco smoke were from spouses (40.8%), the workplace (36.8%) and public areas (26.3%), respectively. After adjusting for other potential risk factors or confounders, females with frequent low-dose passive smoke exposure (${\leq}7$ hours per week) from a spouse or workplace had adjusted odds ratio 3.77 (95%CI=1.11-12.82) and 4.02 (95%CI=1.04-15.50) higher risk of breast cancer compared with non-smokers, respectively. However, this study did not find any association of breast cancer risk in high dose passive tobacco smoke exposure, or a dose response relationship in cumulative passive tobacco smoke exposure per week, or in the active smoker group. In conclusion, passive smoke exposure may be one important risk factor of urban female breast cancer, particularly, from a spouse or workplace. This risk factor highlights the importance of avoiding tobacco smoke exposure as a key measure for breast cancer prevention and control.

Metal Concentrations in Rats and Fetuses Treated by Herbal Decoction, Samultang (사물탕투여가 임신랫드의 모체 및 태자에 미치는 영향 -유해금속(As, Cd, Pb, Hg)과 양-반응관계를 중심으로-)

  • Shin, Heon-Tae;Park, Hae-Mo;Lee, Sun-Dong
    • Journal of Society of Preventive Korean Medicine
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    • v.13 no.2
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    • pp.77-87
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    • 2009
  • Purpose : To evaluate the effects of Samultang(SMT) on the metals in the dams and fetuses Method : SMT(Decoction) was administered orally using different concentrations to pregnant Sprague-Dawley rats for 20days after being assigned randomly to 5 groups. Each group has 11 dams. Pregnant rats were sacrificed at the 20th day of gestation and metal concentration in the dams and fetuses was observed using a ICP-MS and mercury analyzer. Results : Hg concentration in the blood of dams was lower in the $SMT{\times}1$, $SMT{\times}2$, $SMT{\times}4$group than VC(Vehicle Control) and Control group. Hg concentration in the organs of dams was lower in the $SMT{\times}1$, $SMT{\times}2$, $SMT{\times}4$ group than VC, Control group. Whereas Cd concentration in the organs of fetuses was getting lower as increasing SMT dose, Hg concentration in the organs of fetuses was getting higher as increasing SMT dose. Discussion and Conclusion : There were not any significant harmful differences of metal concentration in the dams and fetuses treated by SMT. Particularly, SMT showed the possibility of efficacy to reduce the concentration of Hg in dams but to increase the concentration of Hg in fetuses. The mechanism of reduction is not yet proven. A hypothesis says there is a possibility of the chelation effect between the essential elements of herbs and heavy metals. Another hypothesis is the possibility of Hg transmission from dam to fetus. Further study should be conducted to make guidelines for the safe use of herbal medicine.

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Effect of p16 on glucocorticoid response in a B-cell lymphoblast cell line

  • Kim, Sun-Young;Lee, Kyung-Yil;Jeong, Dae-Chul;Kim, Hak-Ki
    • Clinical and Experimental Pediatrics
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    • v.53 no.7
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    • pp.753-758
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    • 2010
  • Purpose: It has been suggested that p16 has a role in glucocorticoid (GC)-related apoptosis in leukemic cells, but the exact mechanisms have yet to be clarified. We evaluated the relationship between the GC response and p16 expression in a lymphoma cell line. Methods: We used p16 siRNA transfection to construct p16-inactivated cells by using the B-cell lymphoblast cell line NC-37. We compared glucocorticoid receptor (GR) expression, apoptosis, and cell viability between control (p16+NC-37) and p16 siRNA-transfected (p16-NC-37) cells after a single dose of dexamethasone (DX). Results: In both groups, there was a significant increase in cytoplasmic GR expression, which tended to be higher for p16+NC-37 cells than for p16- NC37 cells at all times, and the difference at 18 h was significant (P<0.05). Similar patterns of early apoptosis were observed in both groups, and late apoptosis occurred at higher levels at 18 h when the GR had already been downregulated ($P$<0.05). Cell viability decreased in both groups but the degree of reduction was more severe in p16+NC-37 cells after 18 h ($P$<0.05). Conclusion: These results suggest a relationship between GR expression and cell cycle inhibition, in which the absence of p16 leads to reduced cell sensitivity to DX.

Toxicity Evaluation of Effluent Gases from a Residental Fire by Rats (연립 주택 화재시 유독가스 방출 특성과 Rats를 이용한 독성평가)

  • Kim, Hong;Kang, Young-Goo;Kim, Dong-Hyun;Jung, Ki-Chang;Lee, Chang-Seop;Kim, Woon-Hyung
    • Fire Science and Engineering
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    • v.16 no.3
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    • pp.12-15
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    • 2002
  • It has long been recognized that exposure to fire-induced toxic gases is a fatal hazard confront-ing people in fires. In this study, an indoor fire experiment was conducted in an unoccupied residential building located in An-san city, Kyoung-gi province, and the composition of effluent gases, which include CO, $CO_2$, $O_2$, $SO_2$, NO and $NO_2$, were measured by a gas analyzer. A group of lab rats were exposed to the toxic gases released from fire, and the blood samples of the rats were gathered every 2 minutes. A toxicity evaluation was conducted by analyzing the concentrations of Glucose, AST(GOT), ALT(GPT), CBC Count and CO(carboxy)-Hb in the blood samples. Shown from the analysis is the does-response relationship between the CO concentration that rats were exposed to and the CO-Hb concentration in rat blood.

Shielding for Critical Organs and Radiation Exposure Dose Distribution in Patients with High Energy Radiotherapy (고 에너지 방사선치료에서 환자의 피폭선량 분포와 생식선의 차폐)

  • Chu, Sung-Sil;Suh, Chang-Ok;Kim, Gwi-Eon
    • Journal of Radiation Protection and Research
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    • v.27 no.1
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    • pp.1-10
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    • 2002
  • High energy photon beams from medical linear accelerators produce large scattered radiation by various components of the treatment head, collimator and walls or objects in the treatment room including the patient. These scattered radiation do not provide therapeutic dose and are considered a hazard from the radiation safety perspective. Scattered dose of therapeutic high energy radiation beams are contributed significant unwanted dose to the patient. ICRP take the position that a dose of 500mGy may cause abortion at any stage of pregnancy and that radiation detriment to the fetus includes risk of mental retardation with a possible threshold in the dose response relationship around 100 mGy for the gestational period. The ICRP principle of as low as reasonably achievable (ALARA) was recommended for protection of occupation upon the linear no-threshold dose response hypothesis for cancer induction. We suggest this ALARA principle be applied to the fetus and testicle in therapeutic treatment. Radiation dose outside a photon treatment filed is mostly due to scattered photons. This scattered dose is a function of the distance from the beam edge, treatment geometry, primary photon energy, and depth in the patient. The need for effective shielding of the fetus and testicle is reinforced when young patients ate treated with external beam radiation therapy and then shielding designed to reduce the scattered photon dose to normal organs have to considered. Irradiation was performed in phantom using high energy photon beams produced by a Varian 2100C/D medical linear accelerator (Varian Oncology Systems, Palo Alto, CA) located at the Yonsei Cancer Center. The composite phantom used was comprised of a commercially available anthropomorphic Rando phantom (Phantom Laboratory Inc., Salem, YN) and a rectangular solid polystyrene phantom of dimensions $30cm{\times}30cm{\times}20cm$. the anthropomorphic Rando phantom represents an average man made from tissue equivalent materials that is transected into transverse 36 slices of 2.5cm thickness. Photon dose was measured using a Capintec PR-06C ionization chamber with Capintec 192 electrometer (Capintec Inc., Ramsey, NJ), TLD( VICTOREEN 5000. LiF) and film dosimetry V-Omat, Kodak). In case of fetus, the dosimeter was placed at a depth of loom in this phantom at 100cm source to axis distance and located centrally 15cm from the inferior edge of the $30cm{\times}30cm^2$ x-ray beam irradiating the Rando phantom chest wall. A acryl bridge of size $40cm{\times}40cm^2$ and a clear space of about 20 cm was fabricated and placed on top of the rectangular polystyrene phantom representing the abdomen of the patient. The leaf pot for testicle shielding was made as various shape, sizes, thickness and supporting stand. The scattered photon with and without shielding were measured at the representative position of the fetus and testicle. Measurement of radiation scattered dose outside fields and critical organs, like fetus position and testicle region, from chest or pelvic irradiation by large fie]d of high energy radiation beam was performed using an ionization chamber and film dosimetry. The scattered doses outside field were measured 5 - 10% of maximum doses in fields and exponentially decrease from field margins. The scattered photon dose received the fetus and testicle from thorax field irradiation was measured about 1 mGy/Gy of photon treatment dose. Shielding construction to reduce this scattered dose was investigated using lead sheet and blocks. Lead pot shield for testicle reduced the scatter dose under 10 mGy when photon beam of 60 Gy was irradiated in abdomen region. The scattered photon dose is reduced when the lead shield was used while the no significant reduction of scattered photon dose was observed and 2-3 mm lead sheets refuted the skin dose under 80% and almost electron contamination. The results indicate that it was possible to improve shielding to reduce scattered photon for fetus and testicle when a young patients were treated with a high energy photon beam.

The apoptotic fragment assay in rat peripheral lymphocytes and crypt cells with whole body irradiation with 60Co ϒ-rays and 50 MeV cyclotron fast neutrons (코발트-60 감마선과 50 MeV 싸이크로트론 고속 중성자선에 전신조사된 랫드의 말초 임파구와 음와 세포의 아포토시스 유도를 이용한 생물학적 선량 측정 모델 개발 연구)

  • Kim, Tae-hwan
    • Korean Journal of Veterinary Research
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    • v.41 no.2
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    • pp.203-210
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    • 2001
  • Here, we compared the effectiveness of 50 MeV($p{\to}RBe^+$) cyclotron fast neutrons versus $^{60}Co$ ${\gamma}$-rays by the apoptotic fragment frequency in both rat peripheral lymphocytes and crypt cells to check a radiobiological endpoint. The incidence of apoptotic cell death was increased in all irradiated groups, and radiation at all doses trigger rapid changes in both crypt cells and peripheral lymphocytes. These data suggest that apoptosis may play an important role in homeostasis of damaged radiosensitive target organ by removing damaged cells. The curve of dose-effect relationship for these data of apoptotic fragments frequencies was $y=0.3+(6.512{\pm}0.279)D(r^2=0.975)$ after neutrons, while $y=0.3+(4.435{\pm}0.473)D+(-1.300{\pm}0.551)D^2(r^2=0.988)$ after ${\gamma}$-rays. In addition, $y=3.5+(118.410{\pm}10.325)D+(-33.548{\pm}12.023)D^2(r^2=0.992)$ after ${\gamma}$-rays in rat lymphocytes. A significant dose-response relationship was found between the frequency of apoptotic cell and dose. These data show a trend towards increase of the numbers of apoptotic cells with increasing dose. Dose-response curves for high and low linear energy transfer (LET) radiation modalities in these studies were different. The relative biological effectiveness (RBE) value for crypt cells was 1.919. In addition, there were significant peaks on apoptosis induction at 4 and 6h after irradiation, and the morphological findings of the irradiated groups were typical apoptotic fragments in crypt cells that were hardly observed in the control group. Thus, apoptosis induction in both crypt cells and peripheral lymphocytes could be a useful endpoint of rat model for studying screening test and microdosimetic indicator to evaluate the biological effects of radiation-induced cell damage.

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Analysis of Chromosomal Aberration Induced by Low Dose of Radiation (저선량방사선에 의한 염색체이상 빈도)

  • Yi, Chun-Ja;Ha, Sung-Whan
    • Radiation Oncology Journal
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    • v.11 no.2
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    • pp.233-240
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    • 1993
  • Chromosomal aberration analysis, as a basis for biological radiation dosimetry, was performed for radiation dose ranges below 150 cGy. The yield, ratio of lymphocytes with dicentric and/or ring chromosomes, was 0, 0, 0.4, 0.5, 0.6, 0.8, 1.8, 5.5, 8.0, and $18.5\%$ for 0,5, 10, 15, 20, 25, 50, 75, 100 and 150 cGy, respectively. The Qdr, ratio of dicentric and ring chromosomes in total lymphocytes, was 0, 0, 0.004, 0.005, 0.006, 0.009, 0.018, 0.055, 0.084 and 0.207, respectively. The Qdr, ratio of dicentric and ring chromosomes in lymphocytes with aberration, was 1.0 for the radiation doses up to 75 cGy and 1.05 and 1.11 for 100 and 150 cGy, respectively. From the results, it seems possible to estimate radiation dose from Ydr when the exposure is 25 cGy or more. All the 5 radiation workers studied, with exposure much less than 1 mSv per month, had chromosomal aberrations. And acentric fragment pairs, in addition to dicentric and ring chromosomes, showed good dose response relationship and so may be useful for biological dosimetry for low dose radiation.

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Clinical Impact of Bronchial Reactivity and Its Relationship with Changes of Pulmonary Function After Asthmatic Attack Induced by Methacholine (기관지 반응성의 임상적 의의 및 메타콜린으로 유도된 천식 발작시 폐기능 변화와의 관계)

  • Ryu, Yon-Ju;Choi, Young-Ju;Kwak, Jae-Jin;Lee, Ji-A;Nam, Seung-Hyun;Park, Chang-Han;Chaon, Saon-Hee
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.1
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    • pp.24-36
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    • 2002
  • Background: Bronchial reactivity is known to be a component of airway hyperresponsiveness, a cardinal feature of asthma, with bronchial sensitivity, and is increments in response to induced doses of bronchoconstrictors as manifested by the steepest slope of the dose-response curve. However, there is some controversy regarding methods of measuring bronchial reactivity and clinical impact of such measurements. The purpose of this study was to evaluate the clinical significance and assess the clinical use by analyzing the relationship of the bronchial sensitivity, the clinical severity and the changes in pulmonary function with bronchial reactivity. Method: A total of 116 subjects underwent a methacholine bronchial provocation test. They were divided into 3 groups : mild intermittent, mild persistent, moderate and cough asthma. Severe patients were excluded. Methacholine PC20 was determined from the log dose-response curve and PC40 was determined by one more dose inhalation after PC20. The steepest slope of log dose-response curve, connecting PC20 with PC40, was used to calculate the bronchial reactivity. Body plethysmography and a single breath for the DLCO were done in 43 subjects before and after methacholine test. Results: The average bronchial reactivity was 38.0 in the mild intermittent group, 49.8 in the mild persistent group, 61.0 in the moderate group, and 41.1 in the cough asthma group. There was a weak negative correlation between PC20 and bronchial reactivity. A heightened bronchial reactivity tends to produce an increased clinical severity in patients with a similar bronchial sensitivity and basal spirometric pulmonary function. There were significant correlations between the bronchial reactivity and the initial pulmonary function before the methacholine test in the order of sGaw, Raw, $FEV_1$/FVC, MMFR. There were no correlations between the bronchial sensitivity and the % change in the pulmonary function parameters after the methacholine test. However, there were significant correlations between the bronchial reactivity and the PEF, $FEV_1$, DLCO. Conclusion: There was weak significant negative correlation between the bronchial reactivity and the bronchial sensitivity, and the bronchial reactivity closely reflected the severity of the asthma. Accordingly, measuring both the bronchial sensitivity and the bronchial reactivity can be of assistance in assessing of the ongoing disease severity and in monitoring the effect of therapy.

Immunohistochemical Studies for TIMP-1 and TIMP-2 Expression after Irradiation in Lung, Liver and Kidney of C57BL/6 Mouse (C57BL/96 Mouse의 폐, 간, 신장에서 방사선조사 후 TIMP-1, TIMP-2의 발현에 대한 면역조직화학적 연구)

  • Noh, Young-Ju;Ahn, Seung-Do;Kim, Jong-Hoon;Choi, Eun-Kyung;Chang, Hye-Sook
    • Radiation Oncology Journal
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    • v.19 no.2
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    • pp.181-189
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    • 2001
  • Purpose : Changes in the balance between MMP and TIMP can have a profound effect on the composition in the extracellular matrix (ECM) and affect various cellular functions including adhesion, migration, differentiation of cells, and fibrosis and invasion and metastasis of cancer cells. Radiation therapy is a popular treatment modality for benign and malignant tumor, but the study for radiation effect on MMP and TIMP is scarce. In the current study, we have examined the expression of TIMP in fibrosis-prone (C57BL/6) mice after radiation. Methods and Materials : Adult female mice of $10\~12$ weeks were used. The whole body were irradiated using a Varian CL-4/100 with 2 and 10 Gy. Immunohistochemical staining was peformed according to Avidin Biotin complex method and evaluated by observing high power field. For TIMP-1, TIMP-2 antibodies, reactivity was assessed in the parenchymal cell and in the stromal cell. The scale of staining was assessed by combining the quantitative and qualiative intensity of staining. Results : TIMP-1 immunoreactivity did not change in lung. But, in liver, TIMP-1 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell. in kidney, TIMP-1 immunoreactivity was localized in cytoplasm of some tubular cell. Temporal variations were not seen. Dose-response relationship was not seen except kidney. TIMP-2 immunoreactivity in lung was a score (++) at 0 Gy and elevated to a score (+++) at 2 Gy. TIMP-2 immunoreactivity was a score (++) in liver at 0 Gy. TIMP-2 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell as same as patterns of TIMP-1 immunoreactivity. The TIMP-2 immunoreactivity in liver was elevated to (+++) at 2 Gy. Immunoreactivity to TIMP-2 in kidney was a score (+++) at 0 Gy and was not changed at 10 Gy. The score of TIMP-2 immunoreactivity was reduced to (++) at 2 Gy. TIMP-2 immunoreactivity was confined to tubules in kidney. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIMP-2 immunoreactivity was not seen. Conclusions : Differences between intensity of expression of TIMP-1 and TIMP-2 in each organ was present. Expression of TIMP was localized to specific cell in each organ. Irradiation increased TIMP-1 immunoreactivity in the liver and the kidney. Irradiation increased TIMP-2 immunoreactivity in the lung. But, in the liver and the kidney, TIMP-2 expression to radiation was irregular. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIHP-2 immunoreactivity was not seen. In the future, we expect that the study of immunohistochemical staining of longer period of postirradiation and quantitative analysis using western blotting and northern blotting could define the role of TIMP in the radiation induced tissue fibrosis.

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