Total body irradiation is operated to irradicate malignant cells of bone marrow of patients to be treated with bone marrow transplantation. Field size of a linear accelerator or cobalt teletherapy unit with normal geometry for routine technique is too small to cover whole body of a patient. So, any special method to cover patient whole body must be developed. Because such environments as room conditions and machine design are not universal, some characteristic method of TBI for each hospital could be developed. At Seoul National University Hospital, at present, only a cobalt unit is available for TBI because source head of the unit could be tilted. When the head is tilted outward by 90$^{\circ}$, beam direction is horizontal and perpendicular to opposite wall. Then, the distance from cobalt source to the wall was 319 cm. Provided that the distance from the wall to midsagittal plane of a patient is 40cm, nominal field size at the plane(SCD 279cm) is 122cm$\times$122cm but field size by measurement of exposure profile was 130cm$\times$129cm and vertical profile was not symmetric. That field size is large enough to cover total body of a patient when he rests on a couch in a squatting posture. Assuming that average lateral width of patients is 30cm, percent depth dose for SSD 264cm and nominal field size 115.5cm$\times$115.5cm was measured with a plane-parallel chamber in a polystyrene phantom and was linear over depth range 10~20cm. An anthropomorphic phantom of size 25cm wide and 30cm deep. Depth of dose maximum, surface dose and depth of 50% dose were 0.3cm, 82% and 16.9cm, respectively. A dose profile on beam axis for two opposing beams was uniform within 10% for mid-depth dose. Tissue phantom ratio with reference depth 15cm for maximum field size at SCD 279cm was measured in a small polystyrene phantom and was linear over depth range 10~20cm. An anthropomorphic phantom with TLD chips inserted in holes on the largest coronal plane was bilaterally irradiated by 15 minute in each direction by cobalt beam aixs in line with the cross line of the coronal plane and contact surface of sections No. 27 and 28. When doses were normalized with dose at mid-depth on beam axis, doses in head/neck, abdomen and lower lung region were close to reference dose within $\pm$ 10% but doses in upper lung, shoulder and pelvis region were lower than 10% from reference dose. Particulaly, doses in shoulder region were lower than 30%. On this result, the conclusion such that under a geometric condition for TBI with cobalt beam as SNUH radiotherapy departement, compensators for head/neck and lung shielding are not required but boost irradiation to shoulder is required could be induced.
Purpose: The modification of radiation-induced apoptosis by EGCG, known as antioxidants or oxidants, was studied in mice spleens irradiated with a lethal dose. Materials and Methods: Male C57BL/6 mice were divided into control, irradiation-only, and EGCG (100 mg/kg i.p. 1 h before irradiation) pretreatment groups. The mice were irradiated with a single whole-body dose of 7 Gy. The apoptosis in the spleens after irradiation of the lethal dose were analyzed by TUNEL assay. In addition, the expression levels of the Bax and Bcl-2 proteins were quantified using a Western blotting method. Results: The induction of apoptosis was detected in the splenic white pulp. The highest level of apoptosis was detected at 8 hours after irradiation. No significant difference was identified by the apoptotic index (53.9% vs. 52.1%, p=0.328) and relative Bax protein expression (0.86 vs. 0.81, p=0.335), between the irradiation-only and EGCG pretreatment group, respectively. However, a lower Bax/Bcl-2 ratio (1.64 vs. 0.97, p=0.037) and higher relative expression level of Bcl-2 protein (0.57 vs. 0.82, p=0.037) was measured in the EGCG pretreatment group. Conclusion: The EGCG pretreatment neither decreased the radiation-induced apoptosis in mice splenocytes, nor induced additional apoptosis.
Objective: Low dose radiation may stimulate the growth and development of animals, increase life span, enhance fertility, and downgrade the incidence of tumor occurrence.The aim of this study was to investigate the antitumor effect and hormesis in an erythrocyte system induced by low-dose radiation. Methods: Kunming strain male mice were subcutaneously implanted with S180 sarcoma cells in the right inguen as an experimental in situ animal model. Six hours before implantation, the mice were given 75mGy whole body X-ray radiation. Tumor growth was observed 5 days later, and the tumor volume was calculated every other day. Fifteen days later, all mice were killed to measure the tumor weight, and to observe necrotic areas and tumor-infiltration-lymphoreticular cells (TILs). At the same time, erythrocyte immune function and the level of 2,3-diphosphoglyceric acid (2,3-DPG) were determined. Immunohistochemical staining was used to detect the expression of EPO and VEGFR of tumor tissues. Results: The mice pre-exposed to low dose radiation had a lower tumor formation rate than those without low dose radiation (P < 0.05). The tumor growth slowed down significantly in mice pre-exposed to low dose radiation; the average tumor weight in mice pre-exposed to low dose radiation was lighter too (P < 0.05). The tumor necrosis areas were larger and TILs were more in the radiation group than those of the group without radiation. The erythrocyte immune function, the level of 2,3-DPG in the low dose radiation group were higher than those of the group without radiation (P < 0.05). After irradiation the expression of EPO of tumor tissues in LDR group decreased with time. LDR-24h, LDR-48h and LDR-72h groups were all statistically significantly different from sham-irradiation group. The expression of VEGFR also decreased, and LDR-24h group was the lowest (P < 0.05). Conclusion: Low dose radiation could markedly increase the anti-tumor ability of the organism and improve the erythrocyte immune function and the ability of carrying $O_2$. Low-dose total body irradiation, within a certain period of time, can decrease the expression of hypoxia factor EPO and VEGFR, which may improve the situation of tumor hypoxia and radiosensitivity of tumor itself.
Kim, Joong-Sun;Lee, Seung-Sook;Jang, Won-Suk;Lee, Sun-Joo;Park, Sun-Hoo;Cho, Soo-Youn;Moon, Chang-Jong;Kim, Sung-Ho;Kim, Mi-Sook
Radiation Oncology Journal
/
v.28
no.3
/
pp.141-146
/
2010
Purpose: We examined the radioprotective effects of 5-androstendiol (5-AED), a natural hormone produced in the reticularis of the adrenal cortex, as a result of intestinal damage in gamma-irradiated C3H/HeN mice. Materials and Methods: Thirty mice (C3H/HeN) were divided into three groups; 1) non-irradiated control group, 2) irradiated group, and 3) 5-AED-treated group prior to irradiation. Next, 5-AED (50 mg/kg per body weight) was subcutaneously injected 24 hours before irradiation. The mice were whole-body irradiated with 10 Gy for the histological examination of jejunal crypt survival and the determination of the villus morphology including crypt depth, crypt size, number of villi, villus height, and length of basal lamina, as well as 5 Gy for the detection of apoptosis. Results: The 5-AED pre-treated group significantly increased the survival of the jejunal crypt, compared to irradiation controls (p<0.05 vs. irradiation controls at 3.5 days after 10 Gy). The evaluation of morphological changes revealed that the administration of 5-AED reduced the radiation-induced intestinal damages such as villus shortening and increased length of the basal lamina of enterocytes (p<0.05 vs irradiation controls on 3.5 day after 10 Gy, respectively). The administration of 5-AED decreased the radiation-induced apoptosis in the intestinal crypt, with no significant difference between the vehicle and 5-AED at 12 hours after 5 Gy. Conclusion: The results of this study suggest that the administration of 5-AED has a protective effect on intestinal damage induced by $\gamma$-irradiation. In turn, these results suggest that 5-AED could be a useful candidate for radioprotection against intestinal mucosal injury following irradiation.
The number of splenic lymphocyte, serum prostaglandin $E_2$ level and natural killer cell activity were assayed after single whole body irradiation of a sublethal dose of $^{60}Co-{\gamma}$ ray to C57BL/6J mice. With a view to knowing the relationships between radiation induced prostaglandin $E_2$ level and the normal natural killer cell activity after natural killer cell-target cell conjugation, The change of normal natural killer cell activity were measured by administration of prostaglandin $E_2$ containing serum from irradiated mice. The results were summarized as follows; 1. The total number of splenic lymphocyte was significantly decreased by irradiation and the number was not affected by indometacin, prostaglandin synthesis inhibitor, treatment. 2. Serum prostaglandin $E_2$ level was increased in irradiated mice, but indometacin treated mice group showed low level of prostaglandin $E_2$. 3. In the case of irradiated mice, natural killer cell activity was not shown any difference between irradiated group and indometacin combined group. But when natural killer cell-target cell conjugations were exposed to the serum of each group during cytotoxic activity assay, whereas the normal natural killer cell activity was significantly decreased by treatment of serum from irradiated mice, the activity was not changed by treatment of indometacin pretreated mice serum. This result indicated that the prostaglandin $E_2$ induced by the radiation inhibited the post-target binding cytolytic process of natural killer activity.
Kim, Sung-Ho;Oh, Heon;Lee, Song-Eun;Kim, Soon-Tae;Jo, Sung-Kee;Hyun, Byung-Hwa;Ryu, Si-Yun;Daynes, Raymond A.
Korean Journal of Veterinary Pathology
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v.1
no.1
/
pp.1-6
/
1997
The cellularity and composition of the spleen lymph node thymus and peripheral blood and tempo of regeneration were studied at various time points after syngeneic bone marrow transplantation(BMT) in C3H/Hen mice. Significant depression of absolute lymphocyte count was noted on week 1 after lethal whole-body irradiation and BMT. In comparison to the lymph node thymus and spleen had an rapid regeneration of cellularity. The distinct cell populations($CD4^+,\;CD8^+,\;CD28^+,\;B220^+) have determined in the lymphoid tissue of mice subjected to irradiation. The relative representation of these subpopulations was significantly different from that in nonirradiated control. $CD4^+\;and\;CD8^+$ cells were present in very low numbers whereas the $B220^+$ cells reached more than normal range at 2 weeks after BMT. The number of $CD4^+$ cells returned to normal relatively soon than $CD8^+$ cell. At week 4 after BMT, the cellularity and composition of spleen lymph node and peripheral blood lymphocyte reached about 50% of the normal range therefore we can choose this time point for the other tests of immune function after BMT.
Purpose : To investigate the regulation of apoptosis and cell cycle in mouse brain irradiation. Materials and Methods : 8-week old male mice, C57B1/6J were given whole body $\gamma-radiation$ with a single dose of 25 Gy using Cobalt 60 irradiator. At different times 1, 2, 4, 8 and 24hr after irradiation, mice were killed and brain tissues were collected. Apoptotic cells were scored by TUNEL assay. Expression of p53, Bcl-2, and Bax and cell cycle regulating molecules; cyclins Bl, Dl, E and cdk2, cdk4, $p34^{cdc2}$ were analysed by Western blotting. Cell cycle was analysed by Flow cytometry. Results : The peak of radiation induced apoptosis is shown at 8 hour after radiation. With a single 25 Gy irradiation, the peak of apoptotic index in C57B1/6J is $24.0{\pm}0.25$ (p<0.05) at 8 hour after radiation. Radiation upregulated the expression of p53/tubulin, Bax/tubulin, and Bcl-2/tubulin with 1.3, 1.1 and 1.45 fold increase, respectively were shown at the peak level at 8 hour after radiation. The levels of cell cycle regulating molecules after radiation are not changed significantly except cyclin D1 with 1.3 fold increase. Fractions of Go-Gl, G2-M and S phase in the cell cycle does not specific changes by time. Conclusion : In mouse brain tissue, radiation induced apoptosis is particularly shown in a specific area, subependyma. These results and lack of radiation induced changes in cell cycle ofter better understanding of radiation response of noraml brain tissue.
Kim, In-Gyu;Park, Seon-Young;Kim, Kug-Chan;Lee, Kang-Suk
Journal of Radiation Protection and Research
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v.22
no.2
/
pp.103-109
/
1997
Adult male rats were exposed to a whole body with a single dose of 1.0, 2.0, 3.0, 5.0, and 7.0 Gy. The animals were sacrificed 48, 72, 96 and 216 hours following exposure. A competitive enzyme linked immunosorbent assay(ELISA) with antigen immobilized on the solid phase has been developed to measure ceruloplasmin in rat serum and complete dose response curves. Ceruloplasmin was purified from the plasma of turpentine treated male rats. Coating of ceruloplasmin had more effectiveness in 10 mM Tris-HCI, 150 mM sodium chloride, pH 7.4 than in 50 mM carbonate/bicarbonate buffer, pH 9.6. The coating range for ceruloplasmin was $70{\sim}140ng$/well. Levels of ceruloplasmin increased to maximum on the $72{\sim}96$ hours after irradiation. Slope of between response and dose was greatest value 96 hours following irradiation. Normal ceruloplasmin levels were not recorded 216 hours following exposure. In 0.1 Gy irradiated group, levels of ceruloplasmin also increased to maximum on the $72{\sim}96$ hours following irradiation. The concentration of this protein remained significantly different from control value, 196 hours after exposure. Ceruloplasmin was identified as one of the major acute phase protein following irradiation and further studies about gene expression and regulation would be necessary for radiation protection.
The protective action of methylene blue against gamma-irradiation was studied with rats. Albino rats were given 360 rads of whole-body gamma-irradiation following an intraperitoneal injection of physiological saline or methylene blue. Male rats given methylene blue (38mg/kg) and the control rats given saline were alive following gamma-irradiation. Serum lactic dehydrogenase (LDH) activity, and LDH isoenzyme patterns in serum and various organs were determined at various time intervals after the exposure. 1) The serum LDH level in both the control and methylene blue-treated rats was increased during the initial phase, but returned to the initial level thereafter. 2) Methylene blue showed a marked delay in the rise of serum LDH at 15 and 64 hours after exposure. 3) The exposure in the control and methylene blue-treated rats resulted in an increase in the relative amount of the more electrophoretically mobile-anodal isoenzyme (band 1) and a decrease in the least mobile-cathodal isoenzyme (band 5) in serum, liver, heart and testis nearly at 40 and 116 hours, respectively. 4) Isoenzyme patterns in serum, liver and testis after exposure were not significantly different between the control and the methylene blue-treated rats. 5) Methylene blue showed a slight delay in alteration of heart tissue LDH isoenzyme patterns after exposure. 6) The increase of serum LDH level after exposure is a reflection of an immediate increase in the H type, band 1 of LDH isoenzymes. 7) It is concluded from this study that methylene blue has a remarkable radioprotective action in the serum LDH activity and in the heart tissue LDH isoenzyme patterns.
This work was undertaken to elucidate some aspects of mechanisms underlying the increased deoxycytidineuria following irradiation in the mice, by observing Dische-positive substances liberated from thissues, the activity of CdR-aminohydrolase of tissues and the CdR excreted in the urine at various times after single whole-body exposure to 400 and 800 R of X-rays. The activity of CdR-aminohydrolase declined markedly at 1 hour in the small intestine and liver, followed by a gradual rise reaching a maximum at 3 days after irradiation. In the case of the spleen and blood, however, only a trace of activity was observed in the control and irradiated animals. The amount of Dische-positive substance liberated from the small intestine postirradiation was elevated from 3 to 12 hours, showing a maximum during 6 to 9 hours after irradiation. On the contrary, the activity of the enzyme in the liver, spleen and kidney was less than one twentieth that of the small intestine, suggesting a prediction that these organs are not attributable to the increased deoxycytidineuria. A maximum deoxycytidineuria was exhibited at 9-12 hours period, attributed a large amount of CdR to the small intestine, which might correlate with the change in the CdR-aminohydrolase activity. Radiation-induced CdR seems to be liberated from the small intestine into the blood when the CdR-aminohydrolase activity declines abruptly. Then, the CdR is rapidly subjected to a filtration in the kidney without undergoing a further degradation pathway in the blood.
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