Relative biological effectiveness of gamma-neutron irradiation with neutron energy of 0.9 MeV

Relative biological effectiveness (RBE) of gamma-neutron radiation with neutron energy of 0.9 MeV was estimated with a reference to rat death. It was shown that RBE of gamma-neutron radiation (the share of neutrons was 67% as related to dose) at LD33/30 and LD100/30 was 2, and RBE of 0.9 MeV neutrons, in experiments with mixed radiation, was 3.1 and 2.86 at LD33/30 and LD100/30, respectively. The value of a maximum dose at which death was not registered during 30 days, was 1 Gy with gamma-neutron radiation and 4 Gy with X-radiation.     

The effects of gamma irradiation on the survival and development of Clonorchis sinensis metacercariae

The effects of gamma irradiation on the survival and development of C. sinensis metacercariae were studied to evaluate the feasibility of irradiation as a control measure for clonorchiasis. Pseudorasbora parva were collected at an endemic river of clonorchiasis and were used for irradiation of the fluke in three schemes. The first (Scheme 1) was irradiation of the isolated metacercariae from the fish followed by infection to experimental rats. The second (Scheme 2) was irradiation of the fish, and then the metacercariae were isolated and infected to rats. The third (Scheme 3) was irradiation on the rat livers after infection with normal metacercariae. Irradiation doses varied from 5 to 100 Gy for Schemes 1 and 2, and 10 to 25 Gy for Scheme 3. The rats were sacrificed 2 to 6 weeks after infection. In Scheme 1, the metacercariae irradiated at 50 Gy failed to survive in the rats after 2 or 6 weeks. However, 1 to 44% of the metacercariae irradiated at 5-30 Gy survived. The estimated LD50 of Scheme 1 was 16.5 Gy. The flukes irradiated in Scheme 2 survived better than those in Scheme 1. The average worm recovery rate in 50 Gy was 28%(7-39% individually). Increasing the dose up to 100 Gy brought a remarkably low survival rate of an average 1%(0-3% individually). The LD50 of Scheme 2 was 47.5 Gy. Worm recovery rates in the 10 Gy group of Scheme 3 were 21-39%, and those in the 25 Gy group were 2% and 34%. Although the metacercariae were irradiated, all of the recovered worms were morphologically normal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Luplatex and its radioprotective properties

In experimental conditions the radioprotective properties of the placental complex Luplatex created in Scientific production complex "Biotechindustry" was studied. In experiments on mice F1(CBA x C57Bl) it was shown that Luplatex injected intraperitoneally in dose 0.5 ml 5-10 min before or after whole body gamma-irradiation with 8 Gy (LD80/30) increased the survival up to 40% as compared to the control group. In white mice protected by oral administration of Luplatex 30 min before exposure to 7.5 Gy, which is absolute minimal lethal dose for this type of mice (LD100/30), the effect was 48.3%.     

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).     

Radiation protection of murine intestine by WR-2721, 16,16-dimethyl prostaglandin E2, and the combination of both agents

The survival of murine intestinal clonogenic cells (ICC) and the survival of mice after whole-body exposure to 137Cs irradiation were used to measure radiation protection by ethiophos (WR-2721), 16,16-dimethyl prostaglandin E2, and the combination of the two. Doses from 2 to 12.5 mg/mouse of WR-2721 increased cell survival linearly from 3.2 +/- 0.3 in controls given 15.0 Gy to 93.1 +/- 5.2 per jejunal circumference. In contrast, 16,16-dm PGE2 increased ICC survival at 15.0 Gy rapidly from 1 to 10 micrograms/mouse, followed by a plateau up to 100 micrograms/mouse. Animal survival at 6 days (LD50/6) increased from 16.3 +/- 0.4 Gy (95% confidence limits) in controls to 20.3 +/- 0.6 Gy in the PG-treated animals. WR-2721 increased the LD50/6 to 26.1 +/- 1.4 Gy. The dose modification factors were 1.25 and 1.60, respectively. The combination of agents increased ICC survival above that seen with each agent alone up to 8 mg WR-2721, above which no additional protection was seen. Animals given 10 micrograms PG plus 10 mg WR-2721 survived longer than with either agent given alone. The LD50/6 was 36.3 +/- 1.8 Gy for a dose modification factor (DMF) of 2.23. In addition, the slope of the probit curve was reduced from those of each agent alone. PG-induced changes in villus epithelial cell morphology and survival may account, in part, for these observations. The results suggest that either the mechanisms for these two types of radiation protectors are different or they act on separate subcellular targets which are critical to survival from radiation injury.     

Differential radioprotection of tissues in C3H/J mice by a combination of 5-hydroxy L-tryptophan with 2-aminoethylisothiuronium bromide hydrobromide.

Differential radioprotection between normal tissues and carcinoma was observed in C3H/J mice treated with a combination of 5-hydroxy L-tryptophan (5-HTP, 100 mg/kg) and 2-aminoethylisothiuronium bromide hydrobromide (AET, 20 mg/kg). Protection to normal tissues was judged by LD50(30) and by radiation induced damage to bone marrow(BM) using clonogenic ability of blood forming stem cells (10 day CFUs) as the criteria. Pretreatment with 5-HTP + AET combination 30 min before whole body gamma radiation (WBGR) enhanced the recoveries of the number of blood forming stem cells in BM of irradiated mice after 0, 7th and 10th day of irradiation. LD50(30) for C3H/J mice was 7.3 Gy and the dose modifying factor (DMF) of 5-HTP + AET combination was 1.76. On the contrary, pretreatment with this combination did not protect the mammary carcinoma transplanted in C3H/J mice, when exposed to 80 Gy soft X-rays.     

The effect of total body gamma-irradiation on mortality, egg production and egg weight of Japanese quails

Male and female Japanese quail 21 weeks old, that were given total body doses of 60Co gamma-rays ranging from 0 to 30 Gy, showed a peak in mortality at 6-8 days post-irradiation. The LD 50/30 was 22.5 Gy, and the LD 90/30 was 26.7 Gy. No differences were evident in mortality between males and females. The reduction in egg production by 30 days post-irradiation was related linearly to the dose, for doses above 6 Gy. The reduction in egg weight (30 days post-irradiation laying period) was also related linearly to the dose.     

Medical-prophylactic properties of the low-molecular-weight chitosan at environmental radiation injury

The possibility of the successful modification of radiation injury by chitosan with low molecular weight (10 kDa) has been established under experimental conditions. The survival of mice increased up to 72.7 and 44.7% respectively at intravenous and intramuscular injection 30 min before gamma-irradiation with a dose 8 Gy (LD97). In guinea pigs the effect was 50-52.6% at intravenous and 40% at intramuscular administration 1-3 h after irradiation with a dose 5 Gy (LD90). Radioprotective efficiency of 10 kDa chitosan is close to that of high-molecular-weight (65-70 kDa) preceding (medicine RS-10 and RS-11).     

Effects of gamma-irradiation on survival, growth and productivity of broiler chicken

In experiments with broiler chicken the influence of gamma-irradiation (137Cs) to survive and productivity of meat poultry was studied. LD50/30 increased from 10.0 to 18.7 Gy with increasing of the age of the irradiated chicken from 3 to 40 days and reduced from 18.3 to 11.9 Gy with increasing of a dose rate from 1.0 to 40.0 Gy/h. As a rule, death of chicken was observed between 4th and 15th days after the exposure; the most early dates of poultry death were found at irradiation dose rate of 40.0 Gy/h. The exposure to doses of 8-20 Gy resulted in stunted growth; in comparison with control group the mass reduced by 22-32 g per each 1 Gy, lowering of meat productivity by 36%.     

Trehalose dimycolate enhances survival of fission neutron-irradiated mice and Klebsiella pneumoniae-challenged irradiated mice

The survival of B6D2F1 female mice exposed to lethal doses of fission neutron radiation is increased when trehalose dimycolate (TDM) preparations are given either 1 h after exposure or 1 day before exposure to radiation. TDM in an emulsion of squalene, Tween 80, and saline was the most effective formulation for increasing the 30-day survival of mice when given 1 day before (90%) or 1 h after (88%) exposure to radiation. An aqueous suspension of a synthetic analog of TDM was less effective at increasing 30-day survival (60%) when given 1 day prior to radiation exposure and not effective when given 1 h after radiation. Mice receiving a sublethal dose (3.5 Gy) of fission neutron radiation and either the TDM emulsion or synthetic TDM 1 h after irradiation were substantially more resistant to challenge with 10, 100, 1000, or 5000 times the LD50/30 dose of Klebsiella pneumoniae than untreated mice.     

Nonuniform irradiation of the canine intestine. I. Effects

To investigate the effects of nonuniform irradiation on the small intestine, we prepared 24 dogs for continent isoperistaltic ileostomies under aseptic surgical conditions and general anesthesia. After a 3-week recovery period, the ileum was catheterized with a fiberoptic endoscope to observe the intestinal mucosa and to harvest mucosal biopsies. The baseline macroscopic and microscopic appearance of the intestinal mucosa was determined. Two weeks later, the ileum was catheterized with a 100-cm soft tube containing 40 groups of three thermoluminescent dosimeters placed at equally spaced intervals, and a dose of either 4.5, 8, 10, 11, or 15 Gy 60Co gamma rays was delivered to the right abdomen (nonuniform exposure). This method allowed a direct and precise assessment of the dose received at 40 sites located in the 100-cm intestinal segment. The intestinal mucosa was again evaluated 1, 4, and 6 days after irradiation. All animals exposed to 4.5 and 8 Gy survived, whereas none survived after 11 and 15 Gy. After exposure to 10 Gy, 60% of the animals died within 4-6 days and 40% survived with symptoms associated with both the intestinal and the hematopoietic syndromes. Crypt cell necrosis, blunting of villi, and reduction of the mucosal lining increased between 1 and 4 days after irradiation, and mucosal damage was correlated with intraintestinal dosimetry at Day 6. The granulocyte counts at Day 4 were significantly lower than baseline level in animals that died within 4-6 days but not in survivors. The present model appears to be realistic and clinically relevant, allowing the concurrent study of the intestinal and hematopoietic effects of high-dose nonuniform irradiation similar to that received by patients during radiation therapy as well as by radiation accident victims.     

Protection of mice against mixed fission neutron-gamma (n: gamma = 1:1) irradiation by WR-2721, 16,16-dimethyl PGE2, and the combination of both agents

The survival of mice after whole-body exposure to a modified fission neutron-gamma field (n: gamma = 1:1) was used to examine radiation protection by WR-2721, 16,16-dimethyl PGE2(DiPGE2), and the combination of both agents. Administration of WR-2721 (453 mg/kg) increased the LD50/30 from 5.24 to 7.17 Gy (DMF = 1.37), whereas pretreatment with DiPGE2 (1.6 mg/kg) increased the LD50/30 to 5.77 Gy (dose modification factor (DMF) = 1.10). The combination of 453 mg/kg WR-2721 and 0.4 mg/kg DiPGE2 resulted in an LD50/30 of 7.33 Gy, yielding a DMF of 1.39. However, no significant difference in protection was obtained with the combination of the two agents compared to that seen with WR-2721 alone.     

Late sequelae of exposure to ionizing radiation with various LET's. Effect of dose rate and fractionation on changes in the life span of rats

In experiments with 2120 albino mongrel rats their life span was followed up after the effect of various types of radiation (for instance, gamma-neutron radiation of 0.9 MeV and gamma- and X-rays) at different exposure schedules (that is, whole-body irradiation with doses from LD0/30 to LD100/30 and fractionated at 24 and 72 hour intervals and dose--rates varying from 0.00042 Gy/min to 1.02 Gy/min). The type of radiation, the dose--rate, single and cumulative doses, the number of fractions and the interval between them were estimated with respect to their contribution to life span shortening.     

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.     

WR2721 protection of bone marrow in 131I-labeled antibody therapy.

The use of phosphorothioate radioprotectors such as WR2721 in radioimmunotherapy is attractive because radiation delivered to tumors is usually separated in time from that delivered to the marrow and most normal organs, making protection of tumors of little consequence. However, to be effective radioprotectors must provide continuous protection against radiation of varying dose rates. To evaluate the potential of radioprotectors in radioimmunotherapy we treated normal mice with graded amounts of WR2721 in combination with an LD90/30 (26 MBq) of 131I-labeled antibody. A regimen of 15 doses of WR2721, 200 mg/kg prior to antibody infusion followed by 100 mg/kg ip every 4 h for a total of 72 h, was the maximum tolerated dosage schedule. With this schedule, treatment with radioprotectors failed to prolong survival or delay myelosuppression from the 131I-labeled antibody. In contrast, this regimen of radioprotector provided partial protection from a single treatment of 10 Gy total-body radiation given at 0.2 Gy/min. Protection 30 min after the final dose of WR2721 was greater than 3 h after the 14th dose (60 min prior to the final dose). These results suggest that the potential role of phosphorothioate radioprotectors in a radioimmunotherapy is limited because of the difficulty in achieving continuous protection with nontoxic amounts of drug and possibly because of a limited effect on low-dose-rate radiation.     

Antioxidant-chemoprevention diet ameliorates late effects of total-body irradiation and supplements radioprotection by MnSOD-plasmid liposome administration

Abstract Many acute and chronic effects of ionizing radiation are mediated by reactive oxygen species and reactive nitrogen species, which deplete antioxidant stores, leading to cellular apoptosis, stem cell depletion and accelerated aging. C57BL/6NHsd mice receiving intravenous MnSOD-PL prior to 9.5 Gy total-body irradiation (TBI) show increased survival from the acute hematopoietic syndrome, and males demonstrated improved long-term survival (Epperly et al., Radiat. Res. 170, 437-444, 2008). We evaluated the effect of an antioxidant-chemopreventive diet compared to a regular diet on long-term survival in female mice. Twenty-four hours before the LD(50/30) dose of 9.5 Gy TBI, subgroups of mice were injected intravenously with MnSOD-PL (100 μg plasmid DNA in 100 μl of liposomes). Mice on either diet treated with MnSOD-PL showed decreased death after irradiation compared to irradiated mice on the house diet alone (P = 0.031 for the house diet plus MnSOD-PL or 0.015 for antioxidant diet plus MnSOD-PL). The mice on the antioxidant-chemoprevention diet alone or with MnSOD-PL that survived 30 days after irradiation had a significant increase in survival compared to mice on the regular diet (P = 0.04 or 0.01, respectively). In addition, mice treated with MnSOD-PL only and surviving 30 days after radiation also had increased survival compared to those on the regular diet alone (P = 0.02). Survivors of acute ionizing radiation damage have ameliorated life shortening if they are fed an antioxidant-chemopreventive diet.     

16,16-Dimethyl prostaglandin E2 increases survival in mice following irradiation

16,16-Dimethyl prostaglandin E2 (DiPGE2), a stable analog of PGE2, increases the LD50/30 survival in CD2F1 male mice when given prior to ionizing radiation. Subcutaneous administration of 40 micrograms of DiPGE2 30 min prior to 60Co gamma irradiation extends the LD50/30 from 9.39 Gy in the control animals to 16.14 Gy in DiPGE2 treated, with a dose reduction factor of 1.72 [95% confidence limits: 1.62, 1.82]. The degree of protection is dependent on both the time of administration and the dose of the prostaglandin. Ten micrograms administered 5 min prior to receiving a lethal dose of 10 Gy provides 90% survival but only 10% survival if administered 30 min prior to irradiation. Experiments to determine the in vivo concentration of DiPGE2 in organs postinjection show increased levels over time, but these are not correlated with protection. At 30 min after injection, as much as 80% of the DiPGE2 present in the spleen and plasma is unmetabolized. These results suggest that the protection results from the physiologic action of DiPGE2 rather than direct in vivo detoxification of radicals.     

The modifying action of the Japanese pagoda tree (Sophora japonica) and pantocrine in radiation lesions

A study was made of the effect of Sophora japonica and pantocrine on irradiated (2.5 Gy) human lymphoblastoid cells. The radioprotective effect was manifested with the preparations injected separately after irradiation. The highest radioprotective effect was produced by the mixture of the preparations, the injection 15 min after irradiation being more effective than preinjection. The protective effect of the agents was studied on mongrel mice after the administration thereof for the purposes of protection protection-and-treatment and treatment. Sophora japonica and pantocrine were shown to increase the survival rate of lethally exposed mice (LD90/30) when administered in a combination 5-15 min before irradiation and when used for the purposes of protection--and--treatment: 53.3% and 50% of animals, respectively, survived by day 30 following irradiation. DMF was 1.25.     

The RBE of 0.85 MeV neutrons on guinea pig mortality

A comparative study was made of the death rate of guinea pigs after neutron (0.85 MeV) and 137Cs-gamma-radiation (0.66 MeV); LD50/30 were 1.58 and 3.44 Gy respectively. CRBE of neutrons was 2.2 as determined by median lethal dose values for guinea pigs.     

Radioprotection by mangiferin in DBAxC57BL mice: a preliminary study

The radioprotective effects of various concentrations (0, 0.25, 0.5, 1, 2, 5, 10, 17.5, 25, 50, 75 and 100 mg/kg b.wt.) of mangiferin (MGN) was studied in the DBAxC57BL mice whole body exposed to 10 Gy of gamma-irradiation. Treatment of mice with different doses of MGN, one hour before irradiation reduced the symptoms of radiation sickness and delayed the onset of mortality when compared with the non-drug treated irradiated controls. The radioprotective action of MGN increased in a dose dependent manner up to 2mg/kg and declined thereafter. The highest radioprotective effect was observed at 2mg/kg MGN, where greatest number of animals survived against the radiation-induced mortality. The administration of 0.5, 1, 2, 5, 10 and 17.5 mg/kg MGN reduced the radiation-induced gastrointestinal death as evident by a greater number of survivors up to 10 days in this group when compared with the DDW + 10 Gy irradiation group. A similar effect of MGN was observed for the radiation-induced bone marrow deaths also. Our study demonstrates that mangiferin, a gluosylxanthone, present in the Mangifera indica protected mice against the radiation-induced sickness and mortality and the optimum protective dose of 2mg/kg was 1/200 of LD50 dose (400 mg/kg) of MGN. The administration of 400 mg/kg MGN induced 50% mortality, therefore LD50 of the drug was considered to be 400 mg/kg.