| Background: Glioma is the most common malignant tumor in central nervous system with high invasiveness and poor prognosis. The overall effec of clinical treatment with surgical resection combined with radiotherapy and chemotherapy is not satisfied. Interstitial radiation therapy plays an important role in comprehensive treatment of glioma.Early experiments show that, 125I-deoxyuridine (125I-5-iodo-2-deoxyuridine, 125IUdR) can inhibit tumor cell growth and animal survival was significantly longer than control group. The previous results showed that in rats the 125IUdR is mainly gathed in brain, but other main organs also have a certain degree of enrichment, and 125IUdR is mainly excreted through the kidneys.On this basis, we try to study the tissue toxicity after injection of 125IUdR in rats, which help us to determine the next step of pre-clinical research schemes and provide the necessary data.Objective: The aim of present study was to employ the effect of growth and development,tissue distribution of indicators ,biochemical function on blood and tissue toxicity after intracranial injection 125IUdR in rats which can provide the necessary data for 125IUdR tumor radiation treatment of cerebral glioma .Methods: 40 healthy SD rats which weight (100±15) grams were divided into four groups randomly, each group were ten. Each rat(except negative control group ) was injected with 125IUdR .High dose group was 925MBq/Kg, middle dose group was 277.5MBq/Kg, low dose group given was 92.5MBq/Kg and the negative control group was treated with 0.5ml normal saline. Twice a month for 3 months. Three days before the injection,each rat was treated with KI water.10 minutes and 30 minutes after the first injection of 125IUdR, histological distribution of 125IUdR was measured by SPECT . Animals were observed daily after dosing, weighed once a week, and calculated the growth rate of animals. 24hours after the last dosing, execute animals, taking blood for blood and biochemical testing, taking heart, liver, spleen, lung, kidney, intestine, stomach, thyroid and other tissues with HE staining to analysis the pathological changes.Bone marrow was observed under the microscope to analyses the proliferation of blood cell. Continue to observe the remaining rats about two months. Employ toxicity levels after extuting.Results: SPECT measurement results show that the 125IUdR main focus in liver, kidney, stomach, thyroid gland, but rarely distributed in other organs. There were no significantly changes in skin, coat color, behavior etc.. among the four test groups. The growth rate of the animals also has no significantly differences between experimental group and negative control group (P> 0.05). Experimental group had no deaths, bleeding and other serious complications. The abnormal weight loss and development had not been seen in the testing rats. Experimental animals excuted in each group showed no significant adhesion and perforation in bowel. The weight of liver and spleen also had no significant statistical difference among the experimental animals (P> 0.05). The thyroid had no significant atrophy or hypertrophy. The results of the HE staining showed that the heart,liver,kidney and other solid organ had no obvious abnormalities in testing rats except an rat in the middle dose group which had liver focal necrosis. Hollow organs such as gastrointestinal mucosa were not observed necrosis, inflammatory cell infiltration, proliferation and other pathological changes. The bone marrow smear had no abnormal changes. Blood test showed an increase in white blood cell test but without statistical significance (P> 0.05).Blood biochemical results showed that the AST and ALT was significantly higher in the 125IUdR injected group (P <0.05), others showed no significant differences. In rats killed two months later, there were no obvious abnormalities of the indicators between the experimental groups and the control group.Conclusion: 1. The dose of 125IUdR used in this experiment had no effect on the growth and development of the rats. 2. The dose of 125IUdR used in this experiment can't cause significant bone marrow suppression , pathological changes in various organs and other side effects. 3. 125IUdR can not cause long-term toxicity. |
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