Effect of co-polymer 2-methyl-5-vinylpyridine and 2-methyl-5- vinylpyridinium-n-oxide radiation induced myelodepression in mice

On the model of cytopenia induced in mice by irradiation with a dose of 4.0 Gy it was shown that injection of examined copolymer (400 mg/kg) 3 h after irradiation exerts positive effect on haemopoietic system: the decrease of damage and acceleration of repair processes.     

Increasing the radioprotective therapeutic efficacy of typhoid vaccine using sexta-anatoxin in combination with the antimetabolite methotrexate]

A typhoid vaccine with sexta-anatoxin delivered to mice 4.5-5 h after gamma-irradiation has a pronounced therapeutic effect: survival rate is 42% with radiation dose of 8.2 Gy (LD85/30) and 19% with radiation dose of 8.7 Gy (LD95/30). The vaccine of 2.5 and 5 mg/kg combined with methotrexate has a more pronounced therapeutic effect increasing the survival rate up to 65% (LD85/30) and up to 35-40% (LD95/30).     

The role of beta-adrenoreceptors in the mechanism of the hemodynamic action and radiation-protective activity of the copolymer of 2-methyl-5-vinylpyridine with 2-methyl-5-vinylpyridinium-N-oxide

In experiment on anesthetized dogs and cats in was shown that the new water-soluble copolymer initiated depressive reaction characteristic for beta-adrenomimetics. This effect was levelled with the help of non-selective adrenoblockator--propranololum. In experiment on dogs the preliminary treatment with propranololum decreased the therapeutic antiradiation efficiency of the copolymer from 68.4 to 8.3%.     

Fertilizing ability in vitro of golden hamster spermatozoa after acute testicular X-irradiation]

The present study is concerned with the effect of radiation to the testis on fertilizing ability in vitro using golden hamster spermatozoa. Male hamsters at 6 and 8 weeks of age were given acute testicular X-irradiation (200 kVp, 20 mA, 0.47-0.48 Gy/min). Spermatozoa were collected from the cauda epididymides at different times after irradiation and then they were suspended in fertilization medium. After preincubation for 4-5 hr, the spermatozoa were cultured with the eggs collected from mature hamsters treated with PMSG-hCG. Fertilized eggs were examined for incidence of sperm penetration and formation of pronuclei at 4-5 hr after insemination. The fertilization rate (47.7%) at the 6th week after irradiation with a dose of 2 Gy was much lower in comparison with the control value (92.6%). However, the fertilization rates at the 3rd and 9th weeks after irradiation were 97.7 and 90.6%, respectively. In these period, no difference was found between the irradiated groups and the control groups. From the changes in sperm concentration after irradiation with a dose of 2 Gy, it was found that the fertilization rate was the lowest at the 6th week. The sensitive stage to radiation during spermatogenesis with reference to the reduction of fertilizing ability after irradiation coincides with that of decrease in the sperm concentration and sperm motility. The results of fertilization rate at the 6th week after different doses of X-irradiation (0.25-6 Gy) indicated that the reduction of fertilization rate is nearly expressed as a dose-response relationship.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose fractionation effects in low dose rate irradiation of jejunal crypt stem cells

Jejunal crypt survival after fractionated total body irradiation of C3H mice given at dose rates of 1.2 or 0.08 Gy/min was studied. The fractionation effect was more pronounced at the high dose rate than at the low dose rate. Analysis of the data according to the linear-quadratic survival curve model yielded an alpha/beta value at 1.2 Gy/min of 13.3 Gy and at 0.08 Gy/min of 96 Gy.     

Effects of single gamma-irradiation on the activity of ornithine decarboxylase in the thymus and pulmonary tissue]

In studying the dose (0.1-6 Gy) and time (2 h to 180 days) dependence of ornithine decarboxylase activity, it was found that deviations from the control were more pronounced in the thymus than in the pulmonary tissue. The radiation effect was a function of dose and time after irradiation. A nonmonotonous type of the dose-response curve was observed 7 days after irradiation: the radiation effect with a low dose (0.1 Gy) was opposite to that with sublethal doses (1-6 Gy).     

The immunity indices of rats after the long-term action of tritium oxide or gamma irradiation

In experiments with Wistar rats, a study was made of the content of antibody-forming cells and cytotoxic activity of normal killers after long-term administration of tritium oxide (3HOH) (370 kBq.g-1 of body mass daily, cumulative dose, 8.1 Gy, and dose rate, 8.5 cGy/day), and after gamma irradiation with corresponding doses. The long-term radiation effect caused a decrease in the immunity indices: the impairment of the immune reactions was more pronounced after the effect of 3HOH than after gamma irradiation. Damages to the immune system of mice and rats after irradiation with similar doses were compared.     

Effect of gemcitabine on the tolerance of the lung to single-dose irradiation in C3H mice.

In an early phase II trial combining gemcitabine (dFdC) and radiotherapy for lung carcinomas, severe pulmonary toxicity was observed. In this framework, the objective of this study was to investigate the effect of dFdC on the tolerance of the lungs of C3H mice to single-dose irradiation. The thoraxes of C3H mice were irradiated with a graded single dose of 8 MV photons; dFdC (150 mg/kg) or saline (control animals) was administered i.p. 3 or 48 h prior to irradiation. Lung tolerance was assessed by the LD50 at 7-180 days after irradiation. For irradiation alone, the LD50 reached 14.45 Gy (95% CI 13.33-15.66 Gy). With a 3-h interval between administration of dFdC and irradiation, the LD50 reached 13.29 (95% CI 12.26-14.44 Gy); the corresponding value with a 48-h interval reached 13.01 Gy (95% CI 11.92-14.20 Gy). Our data also suggested a possible effect of dFdC on radiation-induced esophageal toxicity. dFdC has a minimal effect on lung tolerance after single-dose irradiation. However, a proper phase I-II trial should be designed before any routine use of combined dFdC and radiotherapy in the thoracic region.     

The radioprotective effect of extracts of Archangelica officinalis Hoffm. and Ledum palustre L. on mice

A single injection of Archangelica officinalis Hoffm. and Ledum palustre L. extracts to mice 5-15 min before irradiation with a median lethal dose increased their survival rate. The most favourable effect was produced by a combination of the two preparations: by day 30 100% of animals survived after a dose of 6 Gy (LD50/30); 70% survived after a dose of 7.5 Gy (LD90/30), and 25% after a dose of 8 Gy (LD100/12). DMF for the extract mixture was 1.48.     

不同剂量的X-射线全身照射对小鼠健康状况及涎腺的影响

目的:通过直线加速器全身照射昆明小鼠建立辐射损伤模型,探索不同放射剂量对小鼠健康状况及涎腺功能和结构的影响。方法:选取八种不同剂量对昆明小鼠行体外全身照射,于照射后一个月内观察小鼠生长情况、体重变化;照射后一周、一个月检测各组小鼠血象的变化;测定放射半数致死剂量;照射后两个月,测定各组小鼠的唾液流量及唾液淀粉酶含量,并对下颌下腺组织切片行HE染色。结果:13Gy和15Gy照射组小鼠的体重逐渐下降,一周后死亡,其余组小鼠体重最终呈增加趋势。X-射线全身照射的半数致死量为10Gy。照射后一周,照射组小鼠的白细胞数目明显降低,与对照组比较有明显统计学差异(P0.01);在其他血象方面,除了7Gy组外,其他照射组与对照组比较也均有统计学差异(P0.05)。照射一个月后,各照射组小鼠的血象均恢复正常。照射后两个月,9Gy组和11Gy组小鼠的唾液流量及唾液淀粉酶含量均显著低于0Gy组,且11Gy组较9Gy组亦明显降低,差异均有统计学意义(P0.05)。随照射剂量的增加,小鼠的下颌下腺腺泡细胞数目逐步减少,结构排列紊乱,组织损伤逐渐加重。结论:X-射线全身照射引起小鼠健康状况受损,免疫功能减低,损伤程度与放射线强度呈剂量依赖性,小鼠半数致死量为10Gy,该剂量适合建立全身放射损伤模型。     

The effect of recombinant human interleukin-1 beta on the repopulation of bone-marrow colony-forming cells in mice subjected to the action of radiation and burns]

The radioprotective and restorative (therapeutic) effects of human recombinant interleukin-1 beta (IL-1 beta) on the population of bone marrow CFU-S of mice, subjected to either sublethal doses of ionising irradiation itself or the same irradiation in combination with thermal burn, are investigated. Both the effects of the agent are registered under both in vitro and in vivo irradiation in semi-, syn- and allogeneic animals. If the irradiation was combined with thermal burn, the "therapeutic" effect of the agent was demonstrated at irradiation dose equal to 3.06 Gy rather than to 6.12 Gy. If the bone marrow cells were irradiated in vitro in dose 3.06 Gy with the following heat shock at 42 degrees C for 10-20 min, the "therapeutic" effect of IL-1 beta was seen only if it was added to cells before rather than after irradiation. The radioprotective effect of IL-1 beta is maintained under in vitro, as well as in vivo conditions in the allogeneic system of transplantation of the CBA donor bone marrow to the C57BL mice.     

Radioprotective effect of pyrazolone derivatives]

The intraperitoneal injection of analgin (1000 mg/kg), antipurine (400 mg/kg), amidopyrine (100 mg/kg) 3 hours before the irradiation of mice in a dose of 800 R led to survival of 30 to 45% of the animals (against 12.5% in control) and to increase in the average duration of life of the animals that perished. 80-95% of mice survived the period of "intestinal deaths" (the 7th day after the irradiation) after combined prophylactic use of purasolone derivatives and cystamine before the irradiation of these animals in a dose of 1050 R. The radioprotective effect of pyrasolone derivatives given in therapeutic doses was less pronounced.     

Radiation-induced myeloid leukemia in C3H/He mice and the effect of prednisolone acetate on leukemogenesis

We found that the incidence of spontaneous myeloid leukemia in C3H/He male mice was less than 1%, but it could be increased considerably by total-body X irradiation. The induction of myeloid leukemia was seen to increase after doses from 0.47 Gy (3%) to 2.84 Gy (23.9%), and then decrease after a dose of 4.73 Gy (13.6%). The administration of prednisolone acetate (synthesized glucocorticoid) after irradiation resulted in a significant increase in the incidence of myeloid leukemia from 23.9 to 38.5% after a dose of 2.84 Gy; however, corticosterone, a glucocorticoid secreted by cells, did not have such an enhancing effect.     

Dose-response relationship for translocation induction in spermatogonia of the crab-eating monkey (Macaca fascicularis) by chronic gamma-ray-irradiation

The induction of reciprocal translocations in spermatogonia of the crab-eating monkey (Macaca fascicularis) by chronic gamma-irradiation (1.8 x 10(-5) Gy/min, about 0.024 Gy/22 h/day) was examined. The frequencies of translocation per cell were 0.15% at 0.3 Gy, 0.27% at 1.0 Gy and 0.33% at 1.5 Gy. The dose-response relationship for translocation yield was a linear one with a regression coefficient (b) of 0.16 x 10(-2). When the slope (b) of the regression line was compared with that at a high dose rate (0.25 Gy/min, b = 1.79 x 10(-2), it was clear that the induction rate of translocations after chronic gamma-irradiation was only about one-tenth of that after high-dose-rate irradiation. Thus, there was evidence for a pronounced dose-rate effect in the crab-eating monkey.     

The influence of chronic and of acute irradiation on the polymorphism of RAPD-markers in offspring for irradiated mice

On mice lines BALB/c and CBA/lac was performed the study of molecular-genetics effects in mice progeny after the chronic (dose rate -0.0017 Gy/day, total dose -0.36 Gy) and acute (dose range 1-3 Gy) exposure of y-radiation on the parents. For variability analysis was used technique of amplification DNA with series of random primers (RAPD-assay). Random primers were used as single primer and in mixture of ones. In this work were held the comparative analysis of the genetic radiosensitivity for stem spermatogonia and spermatides. After the acute exposure the dose dependence for levels of polymorphism of RAPD-markers were obtained. After the chronic irradiation, significant differences from control group were obtained only by use primers mixture M1. Comparative analysis of the genetic radiosensitivity of different stages of mice spermatogenesis are display is similar sensitivity of stem spermatogonia and spermatides after doses of irradiation 1 Gy and 3 Gy. Indicated that after irradiation by dose 2 Gy, spermatogonia are more sensitivity than spermatides.     

Antioxidative and radiation modulating properties of guanosine-5'-monophosphate

Employing enhanced chemiluminescence in luminol-p-iodophenol peroxidase system and coumarine-3-carboxylic acid, it was shown that guanosine-5'-monophosphate (GMP) appreciably reduces formation of H?O? and hydroxyl radicals induced by x-ray irradiation. Using immunoenzyme assay, we revealed that GMP lowered 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) formation in DNA in vitro after irradiation. The results of survival test have shown that mice being injected intraperitoneally with GMP after irradiation with a dose of 7 Gy had better survival rate than the control mice. GMP reduced leucopoenia and thrombocytopenia in irradiated mice. Obtained results give premises that GMP may be promising therapeutic agent for treatment of radiation injuries.     

低水平辐射诱导的细胞遗传学适应性反应

先用0.01GY x-射线(剂量率:0.01GY/分)体外照射人、兔外周血,经不同时间后再用1.5GY X-射线(0.44GY/分)照射,发现在G_0、G_1、S和G_2期受0.01GY X-射线照射后再给大剂量照射者,其染色体畸变率明显低于单纯受1.5GY X-射线照射组(P<0.01)。这一适应性反应能持续3个细胞周期,在接受小剂量照射后超过3个细胞周期再受大剂量照射者,染色体畸变率未见减少。若在第三细胞周期以后再次给予小剂量照射,可再次诱导适应性反应。用小鼠整体小剂量照射后骨髓细胞和生殖细胞亦出现这种适应性反应。另外也探讨了不同剂量和不同剂量率的预先照射对适应性反应的影响。     

Apoptosis in HeLa Hep2 cells is induced by low-dose,low-dose-rate radiation

Radioimmunotherapy with radiolabeled antibodies may cause inhibition of the growth of epithelial tumors, despite low total radiation doses and comparatively low radiosensitivity of epithelial tumor cells. The induction of apoptosis by low-dose radiation, such as delivered in radioimmunotherapy, was investigated in vitro in human HeLa Hep2 carcinoma cells. The cultured cells were exposed to defined radiation doses from a (60)Co radiation therapy source. The radiation source delivered 0.80 +/- 0.032 (mean +/- SD) Gy/min and the cells were given total doses of 1, 2, 5, 10 and 15 Gy. Using fluorescein-labeled Annexin V, followed by flow cytometry and DNA ladder analysis, apoptotic cells were detected and quantified. Radiation doses below 2 Gy did not cause any significant increase in apoptosis. Compared to control cells, apoptosis was pronounced after 5-10 Gy irradiation and was correlated to the radiation dose, with up to 42 +/- 3.5% of the cells examined displaying apoptosis. Clonogenic assays confirmed significantly decreased viability of the cells in the interval 2 to 10 Gy with low-dose-rate radiation, 60 +/- 2% compared to 2 +/- 2%. Lethal effects on the tumor cells were also evaluated by an assay of the cytotoxic effects of the release of (51)Cr. Significant cytotoxicity, with up to 64 +/- 6% dead cells, was observed at 5 Gy. Similar results were obtained when the dose rate was reduced to 0.072 +/- 0.003 Gy/min (mean +/- SD). In the case of the (137)Cs source, the dose rate could be reduced to 0.045 Gy/h, a level comparable to radioimmunotherapy, which induced significant apoptosis, and was most pronounced at 72-168 h postirradiation. It can be concluded that in vitro low-dose and low-dose-rate radiation induces apoptosis in epithelial HeLa Hep2 cells and thus may explain a mechanism by which pronounced inhibition of growth of HeLa Hep2 tumors at doses used in radioimmunotherapy has been obtained previously.     

The importance of abrogation of G2-phase arrest in combined effect of TRAIL and ionizing radiation

BACKGROUND: In this work we studied the relationship between the enhanced expression of DR5 receptor and the effect of combination of TRAIL and ionizing radiation on cell cycle arrest and apoptosis induction in human leukemia cell line HL-60. MATERIAL AND METHODS: DR5, APO2.7 and cell cycle were analyzed by flow cytometry. Proteins Bid and Mcl-1 were analyzed by Western-blotting. For clonogenic survival, colony assay on methylcellulose was used. RESULTS: Ionizing radiation caused significantly enhanced positivity of DR5 receptors 24 h after irradiation with high doses (6 and 8 Gy). An increase of DR5 receptor positivity after a dose of 2 Gy was not statistically significant and application of TRAIL 48 h after irradiation did not increase the apoptosis induction. However, a decrease of radiation-induced G(2) phase arrest and an increase of apoptosis were observed when TRAIL was applied 16 h before irradiation with the dose of 2 Gy. Incubation with 6 microg/l TRAIL for 16 h reduced D(0) value from 2.9 Gy to 1.5 Gy. The induction of apoptosis by TRAIL was accompanied by Bid cleavage and a decrease of antiapoptotic Mcl-1 16 h after incubation with TRAIL. CONCLUSION: TRAIL in concentration of 6 microg/l applied 16 h before irradiation by the dose of 1.5 Gy caused the death of 63% of clonogenic tumor cells, similarly as the dose of 2.9 Gy alone, which is in good correlation with the enhanced apoptosis induction.     

Suppression of thymic lymphoma induction by life-long low-dose-rate irradiation accompanied by immune activation in C57BL/6 mice

The induction of thymic lymphomas by whole-body X irradiation with four doses of 1.8 Gy (total dose: 7.2 Gy) in C57BL/6 mice was suppressed from a high frequency (90%) to 63% by preirradiation with 0.075 Gy X rays given 6 h before each 1.8-Gy irradiation. This level was further suppressed to 43% by continuous whole-body irradiation with 137Cs gamma rays at a low dose rate of 1.2 mGy/h for 450 days, starting 35 days before the challenging irradiation. Continuous irradiation at 1.2 mGy/h resulting in a total dose of 7.2 Gy over 258 days yielded no thymic lymphomas, indicating that this low-dose-rate radiation does not induce these tumors. Further continuous irradiation up to 450 days (total dose: 12.6 Gy) produced no tumors. Continuously irradiated mice showed no loss of hair and a greater body weight than unirradiated controls. Immune activities of the mice, as measured by the numbers of CD4+ T cells, CD40+ B cells, and antibody-producing cells in the spleen after immunization with sheep red blood cells, were significantly increased by continuous 1.2-mGy/h irradiation alone. These results indicate the presence of an adaptive response in tumor induction, the involvement of radiation-induced immune activation in tumor suppression, and a large dose and dose-rate effectiveness factor (DDREF) for tumor induction with extremely low-dose-rate radiation.