Sublethal Doses Of Gamma Radiation Research Articles

Mitigating effects of sublethal and lethal whole-body gamma irradiation in a mouse model with soluble melanin

The field of radiation countermeasures is growing, however, currently there are no effective and non-toxic compounds which could be administered orally to the individuals post exposure to high doses of ionising radiation. The pigment melanin is ubiquitous through all kingdoms of life and provides selective advantage under radiation stress through its role as a chemical and physical shield, and its capacity to respond and react to exposures. Soluble allomelanin was administered to mice following whole-body exposure to lethal or sublethal doses of gamma radiation to determine its capacity to mitigate the effects of acute radiation syndrome, and its utility as a radiation countermeasure. Allomelanin has shown a trend to improve survival post an 8 Gy sublethal radiation exposure when administered up to 48 h post-irradiation. Furthermore, it improved median and overall survival to a 10 Gy lethal radiation exposure, specifically when administered at 24 h post-irradiation. Histological analysis on the jejunum region of the small intestine of this treatment group indicated that alterations of the mucosal and submucosal architecture, and disruption of the lymphatic system associated with lethal radiation exposure were mitigated when allomelanin was administered at 24 h post-irradiation. Based on this work soluble allomelanin derived from a fungal source could serve as an easily sourced, cost-effective, and viable countermeasure to accidental radiation exposure and merits further investigation.

Evaluation of Lipid Peroxidation under Immobilization Stress in Irradiated Animals in Experiment

BACKGROUND: For many years, the world community has been concerned with the problem of the consequences of radiation exposure on the human body. A wide range of possible variants of radiation effects on humans and biota determines the range of necessary pharmacological means of protecting the organism and populations. In the mechanisms of the formation of radioresistance, the leading role is assigned to the processes of lipid peroxidation (LPO) and the antioxidant (AO) system. The study of the effect of such factors as radiation and immobilization stress on the body separately and in combination is relevant since the modern conditions of human habitation are characterized by high urbanization, physical inactivity, and a complex radioecological situation in a number of regions. AIM: The aim of the study was to study the role of free radical oxidation in the tissues of the adrenal glands and immunocompetent organs and cells under the combined effect of a sublethal dose of gamma radiation and immobilization stress in the experiment. MATERIALS AND METHODS: The work was carried out on 40 male Wistar rats: I-control; II-subjected to immobilization stress after 1 h; III-exposed to gamma irradiation; and IV-tested combined effects (immobilization stress and gamma radiation). Before the exposure, there was topometric-dosimetric preparation of the experimental animals. To this end, the object was placed on an isocentric therapeutic desk of Terasix X-ray simulator (Czech Republic), which is similar to the therapeutic desk of the γ-irradiator by its construction and parameters. RESULTS: The results obtained make it possible to assess the role of free radical oxidation under the combined action of ionizing radiation at a sublethal dose and immobilization stress in the experiment. The combined effect was accompanied by the accumulation of diene conjugates and malondialdehyde products in homogenates and the development of double oxidative stress in the test objects. The dominant role of ionizing radiation was revealed under the combined effects of immobilization stress and radiation factor. CONCLUSIONS: In animals of the 4th group, the state of oxidative-metabolic processes was characterized by overproduction of LPO products and subsequently by depression of AO defense. The urgency of continuing research on the combined effects of radiation and stress factors on public health and taking measures to eliminate negative effects on the population seems to be undoubted.

Melatonin-Caffeine Combination Modulates Gamma Radiation-induced Sperm Malformations in C57BL/6 Male Mice at Sublethal Dose of Gamma Radiation.

Aims:The aim of this study was to assess the protective effect of the melatonin–caffeine combination against γ radiation-induced alterations in the morphological characteristics of sperms.Settings and Design:C57BL/6 male mice (n = 30) were randomly divided into five groups: control, radiation (2 Gy), melatonin (100 mg/kg body wt.) + radiation (2 Gy), caffeine (30 mg/kg body wt.) + radiation (2 Gy), melatonin–caffeine (100–30 mg/kg body wt.) + radiation (2 Gy).Materials and Methods:All the mice were sacrificed 24 h postirradiation, and cauda epididymis was collected. In this study, sperm concentration along with any abnormality in their morphology (amorphous heads, pinheads, hookless, coiled tails, midpiece defect, and tail-less) was observed in the control and treatment group of animals.Results:Radiation exposure (2 Gy) considerably decreases the sperm count when compared with the control group. However, pretreatment with melatonin and melatonin–caffeine combination before gamma irradiation increased the sperm count (P < 0.05), but with caffeine alone could not produce a significant difference. The higher rate of abnormal sperms was observed in the γ-irradiated mice when compared with the control group (P < 0.05). Besides, the numbers of sperm that are hookless and coiled tails were significantly increased after irradiation. Melatonin significantly reduced the number of sperm with amorphous heads and coiled tails. Melatonin–caffeine combination further reduced sperm malformations when compared with the melatonin + 2 Gy radiation and caffeine + 2 Gy radiation group.Conclusions:This study suggests that caffeine exerts a protective effect when given in combination with melatonin against gamma irradiation in sperms of C57BL/6 mice and could be a potent combination for the development of radioprotector.

Changes in Differential Expression of Genes in Normal and Metabolically Suppressed Mice in Response to Radiation.

Differential gene expression profiles of mice in active and metabolically suppressed states were evaluated in response to a sublethal dose of gamma radiation to identify the beneficial protective effects of suspended animation. Results demonstrated that nearly 90% suppression of metabolic functions in mice lead to significant changes in gene expression profile of different metabolic pathways responsible for adaptation and maintenance of homeostasis in the new physiological state of suspended animation. This state was found sustainable during 18 hrs of experiment and can be reversed back to the normal active state without any visible effects on physiological and behavioral functions of mice. Gene expression during induced states was gathered via Illumina microarray methods. Further analysis of differential gene expressions yielded a result that a hypometabolic state may be responsible for short term and long-term radioprotection.

Sensitization to TRAIL and Radioprotective Effect of NCoumaroyl Tyramine Diacetate from Tinospora Cordifolia Induces Apoptosis and Inhibits Neoangiogenesis to Act as an Anti-Cancer Compound.

Tumor cells show differential sensitivity to cell death induced by TRAIL and also develop resistance to conventional radiation therapy along with several side effects being cytotoxic to normal cells. In this present study, we are focusing on tumor sensitization and radioprotective properties of a novel Phyto-compound isolated, purified from hexane extract and structurally identified as N- Coumaroyl tyramine diacetate (N-CTD), from T.cordifolia. We have isolated a novel small molecule characterized as N- coumaroyl tyramine diacetate from T.cordifolia. Trypan blue exclusion assay was used to study the tumor sensitization effect of N-CTD on TRAIL-resistant cells. The flow cytometric analysis was used to analyze the efficiency of N-CTD to induce apoptosis in TRAIL- resistant cells. To assess the radioprotective effect of N-CTD, the tumor-bearing mice were treated with N-CTD and irradiated with gamma radiation. The survival rate and its effect on peritoneal angiogenesis were studied. Pre-treatment with N-CTD sensitized TRAIL – resistant cells to TRAIL- mediated cell death. Flow cytometric analysis showed increased death in TRAIL- resistant cells upon combinatorial treatment. When a single dose of N-CTD combined with the sub-lethal dose of gamma radiation was initiated, the result showed a substantial decrease on peritoneal angiogenesis with increased survivability, decreased cell number and ascites volume in tumor-bearing mice treated with N-CTD. Further, the effect was studied in terms of MVD and presence of CD31 endothelial cell marker. The results were promising to prove that N-CTD is a potential small molecule with antiangiogenic, tumor sensitization and radioprotective effect; the same can be exploited for human applications.

THE COMBINED EFFECTS OF SUBLETHAL DOSE OF RADIATION AND COAL-ROCK DUST ON PRODUCTS OF LIPID PEROXIDATION IN RATS

Ponte Academic JournalMay 2016, Volume 72, Issue 5 THE COMBINED EFFECTS OF SUBLETHAL DOSE OF RADIATION AND COAL-ROCK DUST ON PRODUCTS OF LIPID PEROXIDATION IN RATSAuthor(s): Oralbek Ilderbayev ,L.E. Chulenbayeva, G.S. Nurmukhambetova, A.K. Musaynova, S.O. Rakhyzhanova, G.O. Ilderbayeva, R.R. Olzhayeva, O.A. UsenovaJ. Ponte - May 2016 - Volume 72 - Issue 5 doi: 10.21506/j.ponte.2016.5.27 Abstract:The aim of this research is to study the role of free radical oxidation in the tissues of adrenal and immune organs and lymphocytes during combined effect of sublethal dose of gamma radiation (6 Gy) and coal-rock dust in remote period of time. Forty male Wistar rats were divided into four groups: I – control; II – exposure to coal-rock dust; III – exposure to radiation; IV – combined exposure of coal-rock dust and radiation. Rats from group III and IV exposed by radiation up to 90 days with 6 Gy once via Teragam Сo60 (Czech Republic). The analyses of lipid peroxidation indicators after the combined action of gamma radiation and coal-rock dust sublethal doses have been carried out. The combined effect was accompanied by the accumulation of products of diene conjugates and malonic dialdehyde lipids peroxidation in the homogenates. Moreover the development of dual oxidative stress in the investigated objects was observed. The enhanced content of lipid peroxidation products indicates that the increase of free radical processes is due to long term effect. The dominant role of ionizing radiation in combined exposure of coal-radiation factor has been revealed. Keywords: radiation, lipid peroxidation, coal-rock dust, combined action. Forty male Wistar rats were divided into four groups: I – control; II – exposure to coal-rock dust; III – exposure to radiation; IV – combined exposure of coal-rock dust and radiation. Rats from group III and IV exposed by radiation up to 90 days with 6 Gy once via Teragam Сo60 (Czech Republic). The analyses of lipid peroxidation indicators after the combined action of gamma radiation and coal-rock dust sublethal doses have been carried out. The combined effect was accompanied by the accumulation of products of diene conjugates and malonic dialdehyde lipids peroxidation in the homogenates. Moreover the development of dual oxidative stress in the investigated objects was observed. The enhanced content of lipid peroxidation products indicates that the increase of free radical processes is due to long term effect. The dominant role of ionizing radiation in combined exposure of coal-radiation factor has been revealed. Keywords: radiation, lipid peroxidation, coal-rock dust, combined action. Forty male Wistar rats were divided into four groups: I – control; II – exposure to coal-rock dust; III – exposure to radiation; IV – combined exposure of coal-rock dust and radiation. Rats from group III and IV exposed by radiation up to 90 days with 6 Gy once via TERAGAM Сo60 (Czech Republic). The analyses of lipid peroxidation indicators after the combined action of gamma radiation and coal-rock dust sublethal doses have been carried out. The combined effect was accompanied by the accumulation of products of diene conjugates and malonic dialdehyde lipids peroxidation in the homogenates. Moreover the development of dual oxidative stress in the investigated objects was observed. The enhanced content of lipid peroxidation products indicates that the increase of free radical processes is due to long term effect. The dominant role of ionizing radiation in combined exposure of coal-radiation factor has been revealed. Keywords: radiation, lipid peroxidation, coal-rock dust, combined action. Download full text:Check if you have access through your login credentials or your institution Username Password

Status of Lipid Peroxidation and the Immune System in the Remote Period after a Sublethal Dose Of Gamma Radiation

We studied the intensity of free radical processes in organs (liver, spleen, thymus, lymph nodes of the small intestine, and adrenal glands) and cells (lymphocytes) and immunity system in the remote period to a sublethal dose of γ‐radiation (6 Gy). To investigate the immunity system and the lipid peroxidation of laboratory animals (white rats) in two series of experiments. All rats were divided into 2 groups: I – controls, II group – animals exposed to radiation.As opposed to the said tissues in hepar, there were material changes. MD sustentation was at the level of intact animals exponent (there is the tendency to rise). Given fact show that there are big compensation abilities of hepatic tissues which enables abnormalities arresting of free‐radical processes induced by the effect of ionized irradiationIn such a manner, at the irradiated rats in the remote period were revealed decrease in the main indicators of immunity, the quantity of T‐lymphocytes, a supressiya of nonspecific phagocytic protection of an organism defense. There was CYC increase in blood serum. Perhaps, it was the result of uprising of organism autoimmune response on conjugated antigen. After the radiation effect, in remote period, there were abnormalities in the peroxidation process of lipids in mainly under investigation immunocompetent organs and tissues.

Dose-dependent hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to sublethal doses of gamma radiation

Due to the production of free radicals, gamma radiation may pose a hazard to living organisms. The high-dose radiation effects have been extensively studied, whereas the ecotoxicity data on low-dose gamma radiation is still limited. The present study was therefore performed using Atlantic salmon (Salmo salar) to characterize effects of low-dose (15, 70 and 280mGy) gamma radiation after short-term (48h) exposure. Global transcriptional changes were studied using a combination of high-density oligonucleotide microarrays and quantitative real-time reverse transcription polymerase chain reaction (qPCR). Differentially expressed genes (DEGs; in this article the phrase gene expression is taken as a synonym of gene transcription, although it is acknowledged that gene expression can also be regulated, e.g., at protein stability and translational level) were determined and linked to their biological meanings predicted using both Gene Ontology (GO) and mammalian ortholog-based functional analyses. The plasma glucose level was also measured as a general stress biomarker at the organism level. Results from the microarray analysis revealed a dose-dependent pattern of global transcriptional responses, with 222, 495 and 909 DEGs regulated by 15, 70 and 280mGy gamma radiation, respectively. Among these DEGs, only 34 were commonly regulated by all radiation doses, whereas the majority of differences were dose-specific. No GO functions were identified at low or medium doses, but repression of DEGs associated with GO functions such as DNA replication, cell cycle regulation and response to reactive oxygen species (ROS) were observed after 280mGy gamma exposure. Ortholog-based toxicity pathway analysis further showed that 15mGy radiation affected DEGs associated with cellular signaling and immune response; 70mGy radiation affected cell cycle regulation and DNA damage repair, cellular energy production; and 280mGy radiation affected pathways related to cell cycle regulation and DNA repair, mitochondrial dysfunction and immune functions. Twelve genes representative of key pathways found in this study were verified by qPCR. Potential common MoAs of low-dose gamma radiation may include induction of oxidative stress, DNA damage and disturbance of oxidative phosphorylation (OXPHOS). Although common MoAs were proposed, a number of DEGs and pathways were still found to be dose-specific, potentially indicating multiple mechanisms of action (MOAs) of low-dose gamma radiation in fish. In addition, plasma glucose displayed an apparent increase with increasing radiation doses, although the results were not significantly different from the control. These findings suggested that sublethal doses of gamma radiation may cause dose-dependent transcriptional changes in the liver of Atlantic salmon after short-term exposure. The current study predicted multiple MoA for gamma radiation and may aid future impact assessment of environmental radioactivity in fish.

Gamma rays induce DNA damage and oxidative stress associated with impaired growth and reproduction in the copepod Tigriopus japonicus

Nuclear radioisotope accidents are potentially ecologically devastating due to their impact on marine organisms. To examine the effects of exposure of a marine organism to radioisotopes, we irradiated the intertidal copepod Tigriopus japonicus with several doses of gamma radiation and analyzed the effects on mortality, fecundity, and molting by assessing antioxidant enzyme activities and gene expression patterns. No mortality was observed at 96h, even in response to exposure to a high dose (800Gy) of radiation, but mortality rate was significantly increased 120h (5 days) after exposure to 600 or 800Gy gamma ray radiation. We observed a dose-dependent reduction in fecundity of ovigerous females; even the group irradiated with 50Gy showed a significant reduction in fecundity, suggesting that gamma rays are likely to have a population level effect. In addition, we observed growth retardation, particularly at the nauplius stage, in individuals after gamma irradiation. In fact, nauplii irradiated with more than 200Gy, though able to molt to copepodite stage 1, did not develop into adults. Upon gamma radiation, T. japonicus showed a dose-dependent increase in reactive oxygen species (ROS) levels, the activities of several antioxidant enzymes, and expression of double-stranded DNA break damage genes (e.g. DNA-PK, Ku70, Ku80). At a low level (sub-lethal dose) of gamma irradiation, we found dose-dependent upregulation of p53, implying cellular damage in T. japonicus in response to sub-lethal doses of gamma irradiation, suggesting that T. japonicus is not susceptible to sub-lethal doses of gamma irradiation. Additionally, antioxidant genes, phase II enzyme (e.g. GSTs), and cellular chaperone genes (e.g. Hsps) that are involved in cellular defense mechanisms also showed the same expression patterns for sublethal doses of gamma irradiation (50–200Gy). These findings indicate that sublethal doses of gamma radiation can induce oxidative stress-mediated DNA damage and increase the expression of antioxidant enzymes and proteins with chaperone-related functions, thereby significantly affecting life history parameters such as fecundity and molting in the copepod T. japonicus.

Bacterial stress response to environmental radiation relating to the Fukushima radiation discharge event, Japan: Will environmental bacteria alter their antibiotic susceptibility profile?

Antibiotic resistance in clinical pathogens in humans may be traced back to resistance mechanisms in environmental bacteria and any factors, which are likely to alter (upregulate) resistance in environmental organisms, is of potential and eventual consequence to human pathogens. Furthermore, sublethal doses of gamma radiation to environmental organisms may cause sublethal stress and a selective pressure, which may lead to mutational events that alter the bacterium's susceptibility profile. A gamma ( γ) radiation simulation experiment was performed to emulate the exposure of four environmental bacteria, including Listeria innocua, Bacillus subtilis, E. coli and Pseudomonas aeruginosa, to levels of radiation in and around Fukushima, Japan, equating to 1, 10 and 100 years equivalence exposure. Alteration to susceptibility to 14 antibiotics was measured as the primary endpoint. There was no significant alteration in the susceptibility of the Gram-positive organisms, whereas both Gram-negative organisms became slightly more susceptible to the antibiotics tested over time. These data indicate that such radiation exposure will not increase the antibiotic resistance profile of these organisms and hence not add to the global public health burden of increased antibiotic resistance in human bacterial pathogens.

Developmental Arrest in Mexican Fruit Fly (Diptera: Tephritidae) Irradiated in Grapefruit

Abstract When holometabolous insect larvae are exposed to a radiation treatment, morbidity or mortality are typically manifested during a major developmental transition, usually a transition involving ecdysis. Thus, early instars fail to develop into later instars or the later instars fail to pupate or pupariate. Over a range of sublethal doses of gamma radiation (increments of 0, 15, 20, 25, and 30 Gy) applied to third-instar Mexican fruit flies, Anastrepha ludens (Loew) (Diptera: Tephritidae), infesting or implanted in grapefruits, Citrus paradisi Macfayden, survival decreased with increasing dose. At all radiation doses, the majority of treated larvae arrested development at pupal ecdysis, the transformation from a cryptocephalic to a phanerocephalic pupa. More than 96% of treated larvae died at, or before, reaching this transition at the highest dose tested (30 Gy). Contrary to expectations, the radiation treatment did not cause atrophy of the imaginai tissues, a result that we attribute to apoptosis.

Prostaglandin E2 Is Rapidly Produced In Response to Bone Marrow Injury and Improves Survival of Primitive Hematopoietic Cells

AbstractAbstract 407Since the hematopoietic system is exquisitely sensitive to environmental and iatrogenic injury, the bone marrow microenvironment likely provides protective mechanisms during times of injury or stress. We have previously demonstrated that prostaglandin E2 (PGE2), which can be produced by many cell types in the bone marrow, targets both the bone marrow microarchitecture and primitive hematopoietic cells when administered systemically to mice (Porter, Frisch et. al., Blood, 2009). Since PGE2 is a local mediator of injury and is known to play a protective role in other cell types, we hypothesized that it could be an important microenvironmental regulator of HSPCs during times of injury. To test this hypothesis, we injured mice with a sub-lethal dose of gamma radiation, 6.5 Gy TBI, and sacrificed mice at varying time points from 1 hour to 6 days post-radiation. Bone marrow supernatant was collected and used for quantification of local PGE2 levels by ELISA. We found that, compared to non-irradiated mice, the PGE2 levels were increased greater than two-fold by 4 hours after irradiation (p=0.0030; n=3–6 mice/group), and these levels remain elevated until at least 6 days after injury (p<0.0001 by ANOVA). These data clearly demonstrate that PGE2 production is rapidly upregulated following bone marrow injury. To determine if HSPCs could be responding to this increase in local PGE2, we sorted Lin− c-Kit+ Sca1+ (LSK) cells from murine bone marrow and assayed the expression of the four PGE2 receptors, EP1-EP4. RT-PCR analysis demonstrated that all four receptors are expressed on LSK cells, suggesting that PGE2 could be acting on these primitive hematopoietic cells during times of injury. We next tested whether supplying additional PGE2 to mice could protect hematopoietic cells after injury. Mice were subjected to 6.5 Gy TBI and were treated with 0.5 mg/kg 16,16-dimethyl-PGE2 (dmPGE2) immediately after radiation and once daily thereafter until time of sacrifice. At 24 hours after radiation injury, mice that were treated with dmPGE2 had greater than 8-fold more surviving LSK cells, a population which still retains HSC repopulating activity in competitive transplantation studies, in their bone marrow compared with vehicle treated mice (n=4/group, p=0.046). Similarly, at 72 hr post-radiation, the dmPGE2 treated mice continued to have almost 2-fold greater numbers of LSK cells remaining viable in their bone marrow compared with vehicle treated mice (n=2–3/group). These data suggest that dmPGE2 treatment after bone marrow injury may provide protection, at least in the days immediately following injury, to primitive hematopoietic cells that remain capable of regenerating the hematopoietic system. To further support this idea, we also pretreated uninjured bone marrow cells in vitro with PGE2 (1 μ M) for 90 minutes and then exposed them to the chemotherapeutic agent cytarabine (Ara-C, 10 μ M for 4 hours). Pretreatment with PGE2 results in lower levels of apoptotic LSK cells compared with vehicle pre-treated LSK cells (30.26% vs. 39.02%; n=9/group; 3 independent experiments; p=0.0012). This result correlates with our in vivo radiation injury data and suggests that PGE2 may target primitive hematopoietic cells and render them more resistant to cell death from injury.Taken together, these results suggest that PGE2, which is released in the bone marrow after radiation exposure, may be an important microenvironmental regulator of HSPC response to injury, by preventing cell death, and/or increasing their recovery. Amplification of this physiological signal by treatment with exogenous PGE2 could provide a beneficial means of protecting hematopoietic cells in clinical situations of hematopoietic system injury and bone marrow transplantation, allowing patients to tolerate bone marrow suppressive treatments or to recover more easily. Further, these results also bring forth a potential concern about the safety of blocking prostaglandin synthesis by using anti-inflammatory medications during times of bone marrow injury. Disclosures:No relevant conflicts of interest to declare.

Effect of paternal exposure to gamma rays on juvenile rat forebrain

We studied the transgenerational effect of the sublethal dose of gamma radiation on the proliferative activity of cells in the rostral migratory stream (RMS) in the brain of neonatal and young progeny of male rats exposed to the dose of 3 Gy 25 days before conception with intact control females. To label proliferating cells, the progeny received bromodeoxyuridine (BrdU) injection before sacrifice. The number of BrdU-positive cells was counted in three parts of the forebrain RMS, i.e. in the vertical arm, elbow and horizontal arm, at the 3rd, 7th, 14th, 21st and 28th postnatal days (P3–P28). In the RMS of control rats' progeny, the number of BrdU + cells transiently decreased at the 7th–14th postnatal days. In the progeny of irradiated rats, the dynamics of the changes was similar to that in the corresponding control groups, however, the number of BrdU-positive cells was significantly higher along the whole RMS at all intervals of investigation. These results suggest that paternal exposure to ionizing radiation induced the genome instability, which manifested itself in the progeny by alteration in proliferative activity or slackening of cell migration in the RMS.

Alteration of lethal effects of gamma rays in Swiss albino mice by Tinospora cordifolia.

Tinospora cordifolia is widely used in Ayurvedic medicines. It is known for its immunomodulatory, antihepatotoxic, antistress and antioxidant properties. It has been used in combination with other plant products to prepare a number of Ayurvedic preparations. The present study was undertaken to evaluate the radioprotective effect of an aqueous extract of Tinospora cordifolia (TC) against (60)Co gamma radiation. Oral administration of TC 5 mg/kg body wt to Swiss albino mice 1 h and 15 days prior to whole body radiation exposure (8 Gy) produced a significant protection in terms of survival percentage. After oral administration of TC 10 mg/kg body wt/day to mice 7 days prior to whole body irradiation (8 Gy) there was no mortality until day 13 and 50% of the animals survived until day 30. Mice exposed to radiation (8 Gy) without TC pretreatment exhibited signs of radiation sickness such as anorexia, lethargy, ruffled hair, diarrhoea and these animals died within 14 days of irradiation. The results from the present study suggest that Tinospora cordifolia has a radioprotective effect in Swiss albino mice, thereby enhancing the survival of mice against a sublethal dose of gamma radiation.

Effect of porphyrins on the hematopoietic recovery of mice treated with gamma-radiation.

Porphyrins are a group of organic compounds involved in a wide spectrum of fundamental biological processes. Non-metallic, naturally occurring and synthetic porphyrin derivatives may produce cytotoxic effects in malignant or normal tissues exposed to visible light. Supra-clinical doses of the photosensitizing porphyrin, Photofrin are hematostimulatory when administered to normal and immunosuppressed inbred mice. To determine if a non-photosensitizing metalloporphyrin has similar hematostimulatory activity, we have synthesized iron (III) hematoporphyrin chloride (FeHp) and administered it to sub-lethally irradiated mice. FeHp (10 mg/kg) given 1 and 4 days or 1, 4 and 7 days following sub-lethal (7 Gy) whole body irradiation significantly increased spleen colony forming units of progenitor cells of the granulocyte-macrophage lineage (CFU-GM) 14 days post-irradiation, relative to irradiated controls. In addition, total splenocyte numbers were significantly increased 17 days post-irradiation in mice that had received FeHp 1 and 4 days post-irradiation. When FeHp was given 24 hours prior to irradiation and again 48 hours or 48 and 96 hours post-irradiation, significant increases in splenic CFU-GM and spleen cell numbers, relative to control mice, were observed 15 days post-irradiation. A non-metallic photosensitizing monomeric fraction of Photofrin, deuteroporphyrin IX, 2,4 (4,2) hydroxyethyl vinyl (HVD) was compared to Photofrin for its ability to influence the hematopoietic recovery of irradiated mice. Only Photofrin but not HVD given in 3 doses (10 mg/kg) 1, 4 and 7 days following irradiation (4.8 Gy) significantly enhanced the recovery of spleen cellularity and splenic CFU-GM. In addition, Photofrin significantly increased bone marrow CFU-GM 7 and 10 days following the sub-lethal dose of gamma-radiation. The mechanism by which certain porphyrins augment hematopoiesis in the mouse is unknown. However, the identification of FeHp as a non-photosensitizing monomeric porphyrin with hematostimulatory activity in vivo, indicates that further study of metalloporphyrins is warranted and may reveal their clinical potential within the context of therapeutically-induced immunosuppression.

Effects of sublethal doses of gamma radiation on the mating ability and spermatophore transfer of Ephestia cautella (Lepidoptera: Pyralidae)

The ability of males of Ephestia cautella to mate and transfer sperms after gamma radiation as 5–6-day old pupae was investigated. The results indicate that gamma radiation had no significant effect on mating, sperm transfer and percentage of egg hatch.

Effect of sublethal doses of gamma radiation on the fecundity, longevity and sterility of adults of Sitotroga cerealella (Olivier) (Lepidoptera, Gelechiidae)

Experiments were carried out to study the effect of sublethal doses of gamma radiation (10-100 krad) on fecundity, longevity and sterility of adults of Silotroga cerealella. The results indicate that fecundity of females decreased as the dosage increased from 10–90 krad. At 100 krad no eggs were deposited. Raising the dose to 100 krad resulted in shortening the longevity to about half the longevity of the untreated moths. When irradiated females mated with similarly irradiated males, a dosage of 20 krad caused 97.17% sterility. A dose of 28 krad induced 96.69% sterility when normal females were mated with irradiated males, while 94.14% sterility resulted when normal males were mated with irradiated females.

An Oxygen Effect for Gamma-Radiation Induction of Radiation Resistance in Yeast

Previous evidence in a lower eukaryote indicated the lack of an oxygen effect for ionizing radiation induction of radioresistance [P. E. Bryant, Nature (London) 261, 588-590 (1976)], suggesting that the signal for induction may be different from that in prokaryotes, where DNA damage by a variety of agents has been shown to induce SOS. type repair and radioresistance. We show here that prior exposure to a sublethal dose of gamma radiation caused induction of radioresistance in Saccharomyces cerevisiae, and that the rate of induction was proportional to the initial dose. Irradiation in oxygen produced a higher rate of increase in resistance, per unit dose, than irradiation in nitrogen, with an oxygen enhancement ratio of 2.8. The maximum level of resistance reached in response to saturating doses was the same regardless of the presence or absence of O2 during the initial irradiation. At less than saturating doses, however, the maximum increase in resistance was higher, per unit dose, following irradiation in the presence of O2 than in its absence. Oxic doses which gave the maximum possible in increase the level of resistance were considerably less than those required to produce the maximum rate of increase in resistance. These results suggest a difference in the level at which DNA damage saturates these processes. These results also indicate that the use of DNA damage as a signal for induction of radiation resistance has probably been conserved during the evolution of prokaryotes to lower eukaryotes.

Fine structure of the A cells of the pars intercerebralis of normal and gamma-irradiated female milkweed bug, Oncopeltus fasciatus (Heteroptera: Lygaeidae).

AbstractNeurosecretory A cells in the pars intercerebralis of O. fasciatus were identified at the ultrastructural level. Fine structural study of the A cells of female insects during the period of production of the first batch of eggs revealed that these cells undergo qualitative and quantitative changes during the first eight days of adult life. The A cells appear to be inactive in the newly emerged females. There is a significant depletion of neurosecretory granules (NSG) in the perikarya in the 2‐day‐old females followed by an increase and decrease in the 4‐ and 6‐day‐old females, respectively. The A cells in the 8‐day‐old females showed an accumulation of NSG. The mitochondrial population increases after adult emergence reaching a peak in the 4‐day‐old females, and then declines gradually in the subsequent age groups. The effect of sublethal dose of gamma radiation on the ultrastructure of the A cells was also investigated. Radiation damage is evident as early as four hours after irradiation with 10 kR. There is considerable swelling of the lysosomes and the membrane system in the A cells of irradiated insects. Synthetic activity of the A cells, based on the distribution of the endoplasmic reticulum, Golgi complex and mitochondria, as well as release of the NSG are apparently inhibited after irradiation. Radiation‐induced damage becomes more conspicuous as post‐irradiation interval increases. It is surmised that the damage to the A cells might have contributed at least in part, to the failure of yolk deposition in the irradiated insects.

Radiation-induced inhibition of RNA synthesis in Tetrahymena pyriformis.

Radiation-induced disturbances in RNA synthesis were investigated in exponentially growing Tetrahymena. Sub-lethal doses of gamma-radiation lead to a transient, dose-dependent decrease in the rate of total RNA synthesis measured by 3H-uridine incorporation, without an alteration of 3H-uridine uptake by the cells. The rate of 3H-uridine incorporation decreases exponentially with dose. In contrast, the duration of inhibition of RNA synthesis is linearly dependent on dose. Target-theory calculations suggest that the sensitive molecule has a molecular weight of about 2 X 10(7) Daltons.