A rat is the most common experimental animal used for the realization of the radiation injury model. The certain thickness of rat skin was prepared by peeling off a rat skin. Radiation level was measured by using this rat skin. Also, The schematic of the formula was made that can predict the radiation absorbed dose (RAD) as a function of the thickness of the rat skin. Consequently, we will provide the RAD information in the realization of in-vitro experimental model regarding the rat's skin thickness by applying the formulas. Moreover, the results from this study can be effectively used for the in-vitro experiment of the rat subcutaneous tissue which was exposed to radiation.
Purpose : To assess the histomorphologic changes in the rat lung injury induced by radiation, to determine whether captopril reduces the rat lung injury and to evaluate change in TNF-${\alpha}$ and TGF-${\beta}$ in rat lung damage by radiation and captopril Methods and material : Right lungs in male Sprague-Dawley rats were divided irradiation alone (10, 20, 30 Gy) or radiation (same dose with radiation alone group) with captopril (500 mg/L). Radiation alone group were sacrificed at twelve hours and eleven weeks after radiation and radiation with captopril group (captopril group) were sacrificed at eleven weeks after radiation with captopril. We examined the light microscope and electron microscopic features in the groups. Results : In radiation alone group, there were patch parenchymal collapse and consolidation at twelve hours after radiation. The increase of radiation dose shows more prominent the severity and broader the affected areas. Eleven weeks after radiation, the severity and areas of fibrosis had increased in proportion to radiation dose given in the radiation alone group. There was notable decrease of lung fibrosis in captopril group than in radiation alone group. The number of mast cells rapidly increased with increase of radiation dose in radiation alone group and the degree of increase of mast cell number and severity of collagen accumulation more decreased in captopril group than in radiation alone group. In radiation alone group, expression of TNF-${\alpha}$ and TGF-${\beta}$ increased according to increase of radiation dose at twelve hours after radiation in both group. At eleven weeks after radiation, expression of TGF-${\beta}$ increased according to increase of radiation dose in radiation group but somewhat decreased in captopril group. In the captopril group the collagen deposition increased but less dense than those of radiation alone group. The severity of perivascular thickening, capillary change, the number and degranulation of mast cells more decreased in the captopril group than in the radiation alone group. Conclusion : It is concluded that the effect of captopril in the rat lungs after radiation was considered to be due to its effect on inhibition of mast cells and reduction of collagen deposition, and captopril may be protect in lung damage after radiation. We observed expression of TNF-${\alpha}$ and TGF-${\beta}$ increased at the early phase after radiation and expression of TGF-${\beta}$ increased in proportion to increase of radiation dose at the chronic phase after radiation. This results will contribute to future investigation in reduction mechanism of captopril in lung damage after radiation.
Purpose : The study was designed to investigate the effect of cis-dichlorodiammineplatinum(II)(cis-DDP) on the radiation-induced cardiomyopathy in the rat. Materials and Methods : The myocardial damage was assessed by histopathologic changes. In radiation alone group, radiation dose ranged from 10-40 Gy X-ray in a single dose and in combined group, cis-dichlorodiammineplatinum(II) at a dose of 6 mg/kg was given intraperitoneally immediately after irradiation of same dose with X-ray alone group. Results : The early changes by radiation included congestion, inflammatory cell infiltrations and fibrosis in myocardial interstitium with focal myocardial necrosis, which was noted in 10 Gy group, Myocardial fibrosis was increased by increasing dose of radiation but myocardial necrosis was not Proportional to radiation dose. cis-DDP alone group showed minimal degeneration of myocardium with surrounded by inflammatory cell infiltrations. In combined group, myocardial fibrosis in 10 Gy group were similar to radiation alone group, but 30 Gy and 40 Gy groups showed severer changes. Electron microscopic examination showed disruption of Z-band and edema of mitochondria with decreased matrix density in 20 Gy radiation group which were severer in 40 Gy radiation group. Combined group showed endothelial changes and disruption of Z-band worse than radiation alone group as well as increased connective tissue, which was considered as a hallmark of late change in radiation-induced heart disease. Conclusion : This results showed minimal enhancement of the radiation-induced cardiomyopathy in rats by cis-DDP.
Purpose : To investigate the caspase-3 expression in the acinar and ductal cells of rat submandibular glands after the irradiation of various doses. Materials and Methods : The male Sprague-Dawley rats weighing approximately 250 gm were used for this study. The experimental group was irradiated with a single absorbed dose of 2, 5, 10, and 15 Gy on the head and neck region. The rats were sacrificed on the 1st, 3rd, 7th, 14th, 21 st, and 28th day after irradiation. The specimens including the submandibular gland were sectioned and observed using histopathological and immunohistochemical methods. Results : The local destruction of the acinar and ductal cells and the karyopyknotic nuclei of the acinar cells were observed in the 2 Gy and 5 Gy irradiation groups later than in the 10 Gy and 15 Gy irradiation groups. And the expression of caspase-3 was prominent only in the ductal cells in the 2 Gy and 5 Gy irradiation groups. Conclusion : This experiment suggests that radiation-induced apoptosis in the ductal cells of rat submandibular glands was induced by a low dose radiation associated with the activation of caspase-3 and radiation-induced necrosis was induced by a high dose radiation.
In order to evalute the effects of radiation on mammalian neuronal system, we have examined the effect of gamma-ray radiation on the monoamine oxidase (MAO) activity in monoaminergic neurons. Following the whole body irradiation, MAO activity in the rat brain was measured as well as in the liver for the comparative studies between the neuronal and nonneuronal system. The effects of some radiation protectors and sensitizers were also examined in addition to the $O_2$ effect. The results can be summarized as follows. 1) The MAO activity of rat brain was minimally affected by the radiation dose up to 1,700 cGy Radiation dose above 2,500 cGy inhibited the brain MAO activity by no less than $l0\%.$ MAO-A form was found to be particularly sensitive to radiation. The liver MAO was somewhat inhibited (by about $5\%$) but hardly dependent on the dose of radiation. 2) The inhibitory effect on the brain was initiated immediately by the radiation dose of 2,500 cGy. On the contrary, for the liver, the inhibitory effect became apparent only 2 days after irradiation. 3) Two days after a dose of 2,500 cGy, Vmax and Km of the brain mitochondrial MAO decreased. For liver, Vmax decreased while Km increased, which indicates the kinetic patterns for the neuronal and nonneruronal systems are not affected similarly by radiation. 4) The effect of several known radiation protectors and sensitizers on MAO activity was tested ut no definite results were obtained. The level of -SH group increased in some degree upon radiation but not by the compounds. 5) MAO activity was not affected by $O_2$ concentration, while an elevated level of lipid peroxidase was found under the same condition. The results described here indicate that characteristics of MAO, one of the most important central nervous system enzymes, are liable to radiation, which is partially differentiated from the liver MAO. Also indicated are that the -SH groups are hardly related to the effect of radiation but the production of the lipid peroxide seems to be somewhat correlated to the effect of radiation.
The alkaline single-cell gel electrophoresis (SCGE) assay, called the comet assay, has been applied to detect DNA damage induced by a number of chemicals and biological factors in vivo and in vitro. The DNA damage was analysed by tail moment (TM) and tail length (TL), which were markers of DNA strand breaks in SCGE. Human, mouse and rat peripheral blood lymphocytes (PBLs) were irradiated with different doses of $^{60}Co$${\gamma}$-rays, e.g. 1, 2, 4, and 8 Gy at a dose rate of 1 Gy/min. A dose-dependent increase in TM (p<0.01) and TL (p<0.01) was obtained at all the radiation doses (1-8 Gy) in human, mouse and rat PBLs. Mouse PBLs were more sensitive than human PBLs which were in turn more sensitive than rat PBLs when the treated dosages were 1 and 2 Gy. However, human PBLs were more sensitive than mouse PBLs which were in turn more sensitive than rat PBLs when the irradiation dosages were 4 and 8 Gy. Data from all three species could be fitted to a linear-quadratic model. These results indicated that there may be inherent differences in the radio-sensitivity among PBLs of mammalian species.
The pathological changes of stomach of the rat following 1,000 rad and 1,800 rad single exposure by Cobalt-60 has been made with 50 experimental rats. The dose of 1,000 rad and 1,800 rad single exposure were equivalent of biologic effect of 2,500 rad in 2 1/2 weeks and 6,000 rad in 6 weeks. Following single exposure, the groups of rat were terminated in 1, 2, 4, 8, 12 weeks intervals and the stomach were fixed to formalin solution immediatly after dissection. The pathological changes were as follows : 1. Following 1,000 rad single exposure, the stomach show only mild to moderate submucosal edema in 4,8,12 weeks group. 1 and 2 weeks group show no changes. 2. Following 1,800 rad single exposure, $32\%(8/25)$ of rats were dead by radiation effect and all other groups of stomach revealed variable pathological changes such as submucosal edema, squamous dysplasia, squamous papilloma as well as squamous cell carcinoma. 3. Optimal tolerance dose to the stomach was $4,500\~5,000$rad when irradiation given by supervoltage. The entire stomach was included within the irradiation field, the dose to the stomach should not exceed 6,000 rad. 4. In conclusion, the radiation injury to the stomach were more direct radiation effects to the gastric mucosa rather than secondary changes of radiation injured vessels.
Chun Mison;Kang Seunghee;Jin Yoon-Mi;Oh Young-Taek;Kil Hoon-Jong;Oh Tae-Young;Ahn Byoung-Ok
Radiation Oncology Journal
/
v.19
no.3
/
pp.265-274
/
2001
Purpose : Proctitis is one of acute complications encountered when radiotherapy was appled to the pelvis. Radiation-induced proctitis represents similar microscopic findings that are observed in inflammatory bowel disease (IBD). Nitric oxide (NO) plays an important role in the inflammatory process and many data suggest a close relationship between NO production and gastrointestinal inflammation. This study was aimed to establish the optimal radiation dose for radiation-induced proctitis in rat and to find a relationship between radiation proctitis and NO production. Materials and methods : Female Wistar rats, weighing from 150 to 220 g, received various doses(10-30 Gy) of radiation to the rectum. On the 5th and 10th day after irradiation, rectal specimens were evaluated grossly and microscopically. In addition, the degree of NO production by irradiation dose was evaluated by study with NOS expression and nitrite production in the irradiated rectal tissue. To evaluate relationship between radiation proctitis and NO, we administered aminoguanidine, iNOS inhibitor and L-arginine, substrate of NOS to rats from 2 days before to 7 days after the irradiation. Results : There were obvious gross and hostological changes after 17.5 Gy or higher radiation dose but not with 15 Gy or less radiation dose. Twenty Gy or higher dose of radiation caused Grade 4 damage in most of rectal specimens which were more likely to be related to the late complications such as fibrosis, rectal bleeding and rectal obstruction. A single fraction of 17.5 Gy to the rat rectum is considered to be an optimal dose to produce commonly experienced proctitis in the clinic. The result demonstrated that severity of microscopic damage of rectal mucosa from irradiation significantly correlated with iNOS over-expression. However, administration of iNOS inhibitor or substrate of iNOS did not influence the degree of rectal damage. Conclusion : A single fraction of 17.5 Gy irradiation to the rat rectum considered to be an optimal dose for radiation induced proctitis model. These results indicated that an excess production of NO contributes to pathogenesis of radiation-induced proctitis in part but was not the direct cause of rectal damage.
Skeletal metastases are common in patients suffering from various primary cancers. Radiopharmaceuticals are an effective option for bone pain palliation. In this work, the radiation absorbed dose of 177Lu-EDTMP radiopharmaceutical was estimated for adult man based on biodistribution data in Wistar rats. The MIRD dose calculation method and the Sparks and Aydogan methodology were applied. The results shows that about 46% of injected activity is cumulated on the surface of the trabecular and cortical bones. Radiation absorbed doses of red bone marrow and osteogenic cells were estimated to about 1.1 and 6.2 mGy/MBq, respectively. The maximum administrated activity was obtained 27 MBq/kg of body weight with an effective dose of 0.23 mSv/MBq. The results were compared with other available data from literature. This study indicated that 177Lu-EDTMP provides therapeutic efficacy for achieving bone pain palliation with low undesired dose to other normal organs.
The effect of radiation on the steroidogenesis of rat ovary was investigated. For this purpose, female rats aged 7-8 weeks were exposed to a single dose of ${\gamma}$ radiation(320 rad or 800 rad) by the cobalt-60. At fourth(day of the first estrus) and eighth(day of the second estrus) days after irradiation, the concentrations of serum steroid hormones were determined by radioimmunoassays (RIA). The correlation between survival rate(Y) and radiation dose(X) was Y=-0.06X+100(r=0.89, n=10). Lethal dose$(LD)_{50(30)}$ and $LD_{20(30)}$ were 833.33rad and 333.33rad respectively. The weights of body and ovary was decreased significantly by the $LD_{50(30)}$ irradiation during the 4 days, but both weights were recovered at day 8. The serum levels of 17a-hydroxyprogesterone(170HP) and estradiol($E_2$) in the irradiated rats were not generally different from those of control. However, the levels of testosterone(T) and 19-norterstosterone(19NT) in the irradiated rat at $LD_{50(30)}$ and $LD_{20(30)}$ radiation doses were decreased, while progesterone levels in serum of the irradiated rats were slightly increased. These results suggest that irradiation may inhibit the first step of steroidogenesis, especially the conversion of P to T, in the rat ovary.
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