Gy Of 60Co Gamma Radiation Research Articles

TL response of Sm-doped MgO to 60Co gamma radiation

The thermoluminescent (TL) response of MgO doped with different rare earths was investigated. The TL material was synthesized by the solution combustion method and sintered at 1173 K; the obtained powders were prepared in pellet form. Before irradiation, the dosimeters were annealed at 623 K for 30 minutes to eliminate any TL signal generated during their manufacture. Independent tests were performed doping the MgO with Tm, Dy, Ce and Sm. The highest TL response was found for Sm-doped MgO (MgO:Sm) reaching the highest sensitivity for 0.4 mol% of Sm. For this sample, the TL response showed linearity from 0.001 to 500 Gy of 60Co gamma radiation. The lower detection limit was found to be equal to 1.17 μGy. The sensitivity of the MgO:Sm prepared dosimeter was approximately 10% the sensitivity of the commercial TLD-100. The TL signal fading was found to be 6% after one month. The deconvolution of the glow curve showed a symmetric peak with a general order kinetics, b, centered at 474 K. These results suggest that this new TL material could be a promising detector to use in diverse dosimetry applications.

Effects of combined ciprofloxacin and Neulasta therapy on intestinal pathology and gut microbiota after high-dose irradiation in mice.

Treatments that currently exist in the strategic national stockpile for acute radiation syndrome (ARS) focus on the hematopoietic subsyndrome, with no treatments on gastrointestinal (GI)-ARS. While the gut microbiota helps maintain host homeostasis by mediating GI epithelial and mucosal integrity, radiation exposure can alter gut commensal microbiota which may leave the host susceptible to opportunistic pathogens and serious sequelae such as sepsis. To mitigate the effects of hematopoietic ARS irradiation, currently approved treatments exist in the form of colony stimulating factors and antibiotics: however, there are few studies examining how these therapeutics affect GI-ARS and the gut microbiota. The aim of our study was to examine the longitudinal effects of Neulasta and/or ciprofloxacin treatment on the gut microbiota after exposure to 9.5 Gy 60Co gamma-radiation in mice. The gut microbiota of vehicle and drug-treated mice exposed to sham or gamma-radiation was characterized by shotgun sequencing with alpha diversity, beta diversity, and taxonomy analyzed on days 2, 4, 9, and 15 post-irradiation. No significant alpha diversity differences were observed following radiation, while beta diversity shifts and taxonomic profiles revealed significant alterations in Akkermansia, Bacteroides, and Lactobacillus. Ciprofloxacin generally led to lower Shannon diversity and Bacteroides prevalence with increases in Akkermansia and Lactobacillus compared to vehicle treated and irradiated mice. While Neulasta increased Shannon diversity and by day 9 had more similar taxonomic profiles to sham than ciprofloxacin-or vehicle-treated irradiated animals. Combined therapy of Neulasta and ciprofloxacin induced a decrease in Shannon diversity and resulted in unique taxonomic profiles early post-irradiation, returning closer to vehicle-treated levels over time, but persistent increases in Akkermansia and Bacteroides compared to Neulasta alone. This study provides a framework for the identification of microbial elements that may influence radiosensitivity, biodosimetry and the efficacy of potential therapeutics. Moreover, increased survival from H-ARS using these therapeutics may affect the symptoms and appearance of what may have been subclinical GI-ARS.

Dosimetric properties of KMgF3:Tb + PTFE

This work presents the results obtained from the dosimetric properties of the new radiation detectors of KMgF3:Tb + PTFE. The thermoluminescent material was obtained by microwave technique. The polycrystalline powder obtained was mixed with polytetrafluoroethylene resin powder in the ratio 2:3 to make dosimeters in pellet form. The thermoluminescent response of these new detectors presented a linear behavior, in the dose range between 1 and 1000 Gy 60Co gamma radiation, the repeatability test in the measurements, during ten cycles of heat treatment, irradiation and readouts, showed ± 3.7% DS, the stability test of thermoluminescent signal, during two months showed that the fading is practically null. For the results obtained, this new detector could be very useful for radiation dosimetry, in clinical applications.

Evaluating the use of nuclear techniques for colonization and production of Trichogramma chilonis in combination with releasing irradiated moths for control of cotton bollworm, Helicoverpa armigera

Gamma radiation was tested as a means of increasing production of the egg parasitoid Trichogramma chilonis Ishii by improving the suitability of host eggs and by stimulating reproduction of the parasitoid females. For manipulation of the host eggs’ suitability, radiation was used to either (a) produce developmentally-inactivated (DI) eggs incapable of hatching, or (b) to produce F1 sterile host eggs. For treatment of the parasitoid females with the intent of stimulating reproduction, parasitoid pupae were exposed to very low dose radiation (250 mGray). For tests on host suitability using radiation-induced DI host eggs, newly-laid (<8 h old) host eggs (Helicoverpa armigera Hubner) were exposed to 300 Gy of 60Co gamma radiation. For tests of F1 sterile host eggs, H. armigera moths were mated with individuals exposed to 250 Gy as pupae. Tests were performed with eggs resulting from all possibilities of normal (N) and sterile (S) ♀ × ♂ matings. Both types of DI host eggs (irradiated or sterile), along with untreated host eggs (controls), were exposed to T. chilonis females, using the following host egg-to-parasitoid ratios: 1:10, 1:30, 1:60 and 1:90. Developmentally-inactivated host eggs exposed to 300 Gy did not differ in suitability from normal host eggs at a 1:10 parasitoid–host ratio, but were significantly more suitable at the higher host–parasitoid ratios. F1 sterile eggs were not significantly different in suitability from normal eggs at a 1:10 host–parasitoid ratio but were marginally better at the higher host–parasitoid ratios. In tests performed using T. chilonis females exposed to low-dose radiation (250 mGy), no effects were observed when cohorts of 5 T. chilonis females were provided with only 50 host eggs, but when more hosts were provided (ratios of 1:30, 1:60 and 1:90), significantly higher rates of parasitization were noted for the parasitoids exposed to low-dose radiation. This effect prevailed using both normal host eggs and DI host eggs exposed to 300 Gy. The stimulatory effect also was noted when F1 sterile host eggs were provided to the irradiated T. chilonis females. These results suggest that release of T. chilonis irradiated with 250 mGy may complement release of irradiated H. armigera moths, which produce sterile F1 eggs that can serve as supplemental hosts in the field and thereby enhance the pest management system.

Parasitism rate and sex ratio of Psyttalia (=Opius) concolor (Hymenoptera: Braconidae) reared on irradiated Ceratitis capitata larvae (Diptera: Tephritidae)

Tests were conducted to evaluate use of irradiated Mediterranean fruit fly (medfly), Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), larvae as factitious hosts for mass-rearing the parasitoid Psyttalia concolor (Szepligeti) (Hymenoptera: Braconidae). In order to prevent the release of the alternative host adults, eclosion from unparasitized larvae must be prevented. Exposure of medfly larvae to 40, 50 or 60 Gy of 60Co gamma radiation showed that 60 Gy was the most effective dose in inhibiting adult medfly eclosion. The most suitable host:parasitoid ratio was found to be three larvae per parasitoid regardless of exposure time. When three larvae per parasitoid were exposed for 3 h, there was no significant difference in parasitism rates using irradiated vs. unirradiated host larvae (16.4 vs. 18%, respectively). Irradiation of host larvae also had no significant effect on the sex ratio of resulting parasitoids. Implementation of this practice will improve the efficiency of mass production and release of this biocontrol agent.

Establishment of the comet assay in the freshwater snail Biomphalaria glabrata (Say, 1818)

The single cell gel eletrophoresis or the comet assay was established in the freshwater snail Biomphalaria glabrata. For detecting DNA damage in circulating hemocytes, adult snails were irradiated with single doses of 2.5, 5, 10 and 20 Gy of 60Co gamma radiation. Genotoxic effect of ionizing radiation was detected at all doses as a dose-related increase in DNA migration. Comet assay in B. glabrata demonstrated to be a simple, fast and reliable tool in the evaluation of genotoxic effects of environmental mutagens.

Upper dose thresholds for radiation-induced adaptive response against cancer in high-dose-exposed, cancer-prone, radiation-sensitive Trp53 heterozygous mice.

Trp53 heterozygous mice are radiation-sensitive and cancer-prone. Groups of 7-8-week-old female Trp53 heterozygous mice were exposed to 4 Gy of 60Co gamma radiation at high (0.5 Gy/min) or low (0.5 mGy/min) dose rate. Other groups received 10 or 100 mGy at low dose rate 24 h prior to the 4-Gy dose. Tumor frequency and latency were measured over the animals' life span. Exposure to 10 mGy prior to 4 Gy resulted in a small (approximately 5%) but significant life-span regain and increased latency (approximately 9%) for all malignant tumors taken together, but 100 mGy further reduced life span slightly (approximately 7%). Latency responses were tumor type-specific. The prior 10-mGy exposure resulted in a small (approximately 7%) regain in latency for lymphomas but no change in latency for spinal osteosarcomas. Increasing the adapting dose to 100 mGy eliminated the increase in lymphoma latency and further reduced life span (approximately 8%). A 10-mGy dose prior to 4 Gy at low dose rate had no effects. Adapting exposures had no significant effect on tumor frequency. We conclude that a single low dose induced a small protective response in vivo in Trp53+/- mice, reducing the carcinogenic effects of a subsequent large, high-dose-rate exposure by increasing tumor latency. The upper dose threshold at which low-dose protective effects gave way to detrimental effects was tumor type-specific, as found previously for spontaneous tumors in these same cancer-prone mice (Radiat. Res. 159, 320-327, 2003). However, the upper dose thresholds appear to be lower (below 100 mGy) for radiation-induced tumors than for the same tumors appearing spontaneously.

Cytogenetic dose–response and adaptive response in cells of ungulate species exposed to ionizing radiation

In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose–responses in fibroblasts from three ungulate species (white-tailed deer, woodland caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1–4 Gy of 60Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1–100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small “adapting” stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment.

Low dose fetal irradiation, chromosomal instability and carcinogenesis in mouse

A study was carried out to see if acute low dose fetal irradiation of mouse could induce long lasting chromosomal anomalies and adult cancers. The abdomen of pregnant Swiss mice was exposed to 0.1–1 Gy of 60Co gamma radiation on day 14 of gestation. The animals were killed 24 h later or allowed to deliver their young. Hemopoietic cell death and chromosomal aberrations were studied in the fetal liver. Chromosomal instability was traced in the 1 Gy exposed group from the fetal liver cells through their CFU-S to postnatal bone marrow. The F1 mice were observed for chromosomal aberrations in the bone marrow and for solid tumor incidence. Irradiation produced a significant dose-dependent increase in the hemopoietic cell death and aberrant metaphases in the fetal liver. The main types of aberrations were chromatid breaks and fragments. The aberrations persisted in the spleen colonies developed from these cells. Their frequency decreased in the postnatal bone marrow, however, showed a significant increase at 12 months of age. Some exposed animals had abnormally high leukocyte counts and after 1 Gy their bone marrow had eight times more polyploid cells than the control. Prenatal exposure also significantly increased the incidence of solid tumors, the ovaries showing the highest risk. It is concluded that a single exposure below 1 Gy of gamma radiation at the early fetal stage of these mice can induce persistent chromosomal instability in the hemopoietic cells, and significantly increase the incidence of solid tumors in adults.

Performance Decrement after Combined Exposure to Ionizing Radiation and Shigella sonnei

Ionizing radiation could increase morbidity from common bacterial infections in military personnel on the modern battlefield. The combined effects of a sublethal dose of ionizing radiation and the bacterial diarrheal agent Shigella sonnei on body weight and forelimb grip strength in mice were assessed over a 30-day period. Individually housed B6D2F1 female mice were divided into four groups: control, sham irradiation + gavage with saline vehicle; 3 Gy 60Co gamma radiation at 0.4 Gy/min radiation + saline gavage; sham irradiation + 1.3 x 10(8) colony-forming units (CFUs) S. sonnei via gavage, administered 4 days postirradiation; and the combination of 3 Gy 60Co gamma radiation + 1.3 x 10(8) CFUs S. sonnei. Behavioral tests were conducted 3 days preirradiation and on days 9, 14, and 22 postirradiation. Body weight was significantly reduced in the radiation + Shigella group on days 5 to 10 postirradiation. Forelimb grip strength was reduced for mice in the radiation + Shigella group on days 9 and 14 postirradiation. These data demonstrate that an exposure to gamma radiation in combination with the bacterial agent S. sonnei can lead to a synergistic loss of body weight and degradation in performance.

Effect of Caffeine on the Genotoxic Effects of Gamma Radiation and 4-NQO in Diploid Yeast

Caffeine is an environmental agent to which people are commonly exposed through medicines, drinks, food items, etc. It has been shown to be mutagenic in a number of test systems. In addition, it has also been shown to modify the mutagenic response of ionizing radiation, UV, and several chemical mutagens in a number of test systems. We have studied the effect of caffeine on gamma radiation and 4-Nitroquinoline 1-oxide (4-NQO)-induced gene conversion in the yeast Saccharomyces cerevisiae D7. Stationary phase cells were either exposed to 100-600 Gy of 60Co gamma radiation or treated with 0.15-0.3 microM 4-NQO (30 degrees C, 1 hour), after which they were plated on synthetic complete or minimal media with or without caffeine. Caffeine concentrations ranged from 5 to 15 mM. The results indicated that caffeine at 5 and 10 mM decreased gamma radiation-induced gene conversion frequencies significantly at 400 and 600 Gy. At 600 Gy, the decrease was about 30% and 50% with caffeine concentrations of 5 and 10 mM, respectively. In contrast, caffeine was found to increase the induced gene conversion frequency when cells treated with 0.15, 0.225, and 0.3 microM 4-NQO were plated on media containing caffeine. The increase with 5, 10, and 15 mM caffeine was approximately 1.5, 2, and 2.5, respectively, times the value of 4-NQO alone. The results indicate that the posttreatment repair processes following gamma irradiation or 4-NQO treatment are modified via different pathways.

Pretreatment with Granulocyte Colony-Stimulating Factor Reduces Myelopoiesis in Irradiated Mice

The purpose of this study was to investigate effects of the treatment prior to irradiation with granulocyte colony-stimulating factor (G-CSF) on hematopoiesis in B10CBAF1 mice exposed to a sublethal dose of 6.5 Gy of 60Co gamma radiation. G-CSF was administered in a 4-day regimen (3 microg/day); irradiation followed 3 h after the last injection of G-CSF. Such a treatment was found to stimulate granulopoiesis, as shown by increased counts of granulocyte-macrophage progenitor cells (GM-CFC) and of granulocytic cells in the femoral marrow and spleen at the time of irradiation. However, postirradiation counts of GM-CFC and granulocytic cells in the marrow of mice pretreated with G-CSF were reduced up to day 18 after irradiation. Interestingly, the D0 values for marrow GM-CFC determined 1 h after in vivo irradiation were 1.98 Gy for controls and 2.47 Gy for mice pretreated with G-CSF, indicating a decreased radiosensitivity of these cells after drug treatment. The inhibitory effects of the pretreatment with G-CSF on the postirradiation granulopoiesis could be attributed to the phenomenon of "rebound quiescence" which can occur after cessation of the treatment with growth factors. Postirradiation recovery of erythropoiesis in the spleen of mice pretreated with G-CSF exhibited a dramatic increase and compensated for the decreased erythropoiesis in the marrow at the time of irradiation. This complexity of the hematopoietic response should be taken into account when administering G-CSF in preirradiation regimens.

Possible Involvement of Tumor Necrosis Factor Alpha in Radiation-Induced Hyperthermia in Rats

Exposure of rats to 1-15 Gy of 60Co gamma radiation induces hyperthermia. Because tumor necrosis factor alpha/cachectin (TNF-alpha) is considered to be an important mediator of the biological response to ionizing radiation, its role in radiation-induced hyperthermia was investigated; in addition, the levels of TNF-alpha in serum before and after radiation exposure were determined. Male Sprague-Dawley rats weighing 250-300 g were irradiated with gamma rays from a 60Co source (10 Gy, 10 Gy/min). Irradiation increased the levels of TNF-alpha in serum. Intraperitoneal (i.p.) doses of 10-50 microg/kg of recombinant human TNF-alpha (hTNF-alpha) induced hyperthermia; i.p. administration of 1-3 mg/kg of indomethacin, an inhibitor of prostaglandin synthesis, or 10-50 microg/kg of polyclonal rabbit anti-human TNF-alpha (anti-hTNF-alpha) attenuated the hyperthermia induced by 30 microg/kg of hTNF-alpha or exposure to 10 Gy of gamma rays. These results suggest that irradiation increases TNF-alpha in serum and that TNF-alpha is involved in gamma-radiation-induced hyperthermia. TNF-alpha and gamma-radiation-induced hyperthermia are mediated by prostaglandins.

Modulation of radiation-induced strand break repair by cisplatin in mammalian cells

Purpose: To investigate the repair of ionizing radiation-induced DNA lesions in human skin fibroblasts in the presence of cisplatin-DNA adducts and to determine the persistence of DNA repair inhibition by cisplatin. Materials and methods: Normal human fibroblasts (AG1522) treated with cisplatin were exposed to 4 Gy 60Co gamma-radiation and assayed for repair of radiation-induced damage under growth-permissive conditions. DNA damage was measured by the fluorescence analysis of DNA unwinding (FADU) and cytokinesis-blocked micronucleus assays. Results: Rejoining of strand breaks caused by 4 Gy radiation in cells without cisplatin pre-treatment appeared to be biphasic with an initial fast component (up to 15 min of repair time) followed by a slower component, and was completed by 90 min. Cisplatin treatment (10 mu g/ml, 30 min) immediately before irradiation had no effect on the fast rejoining component, but inhibited the slow component (p 0.01). The same cisplatin treatment 24 h prior to irradiation inhibited both slow and fast components (p 0.01). In contrast, decreasing the cisplatin exposure to 1.0 mu g/ml for 30 min, 24 h prior to irradiation, resulted in an increased amount of strand break repair at each time point measured compared with irradiated control cells. This mild cisplatin treatment (95% survival) also resulted in a reduction of radiation-generated micronuclei indicating an adaptive response. Conclusions: Cisplatin used in combination with ionizing radiation can produce differential cellular responses depending upon the severity of the cisplatin treatment and the time interval between cisplatin and radiation exposures.

The Antioxidant Trolox Enhances the Oxidation of 2′, 7′-Dichlorofluorescin to 2′, 7′-Dichlorofluorescein

The use of antioxidants to prevent intracellular free radical damage is an area currently attracting considerable research interest. The compound 2′,7′-dichlorofluorescin diacetate (DCFH-DA) is a probe for intracellular peroxide formation commonly used in such studies. During our studies we unexpectedly found that incubation of Trolox, a water soluble vitamin E analog, with DCFH-DA in cell-free physiological buffers resulted in the deacetylation and oxidation of DCFH-DA to form the fluorescent compound, 2′,7′-dichlorofluororescein (DCF). The reaction was time-, temperature-, and pH-dependent. Fluorescence intensity increased with an increase in either Trolox or DCFH-DA concentration. These results indicate that even at physiological pH, DCFH-DA can be deacetylated to form 2′,7′-dichlorofluorescin (DCFH). DCFH can then be oxidized to DCF by abstraction of a hydrogen atom by the phenoxyl radical of Trolox. Exposure of the reaction mixture to 10 Gy of 60Co gamma radiation greatly increased production of DCF. Antioxidant compounds reported to “repair” the Trolox phenoxyl radical (e.g., ascorbic acid, salicylate) can also prevent the Trolox-induced DCFH-DA fluorescence. However, compounds that cannot repair the Trolox phenoxyl radical (e.g., catechin) or can themselves form a radical (e.g., uric acid, TEMPOL) either have no effect or can increase levels of DCF. These results demonstrate that experimental design must be carefully considered when using DCFH-DA to measure peroxide formation in combination with certain antioxidants.

Treatment of mice with a novel antineoplastic agent taxol before irradiation increases the frequency of micronuclei in the bone marrow

The frequency of micronucleated polychromatic erythrocytes (MPCE) and the normochromatic erythrocytes (MNCE) and polychromatic and normochromatic erythrocyte ratio ( P N ratio) was studied at 12, 24 and 36 h postirradiation in the bone marrow of male mice treated or not with taxol before exposure to 0–4 Gy of 60Co gamma radiation. The frequency of MPCE increased with the increase in radiation dose in a dose-related manner in the irradiated control group. A peak frequency of MPCE was observed at 24 h postirradiation in irradiated control group. The pattern of increase in MNCE was similar to that of MPCE except that a highest number of MNCE was scored at 36 h postirradiation. Taxol administration to animals before irradiation resulted in a significant elevation in the frequency of MPCE and MNCE at all the postirradiation time periods studied. This increase was dose related as observed in the irradiated control group. Irradiation resulted in a dose-dependent decline in the P N ratio at all the postirradiation time periods studied. The P N ratio was significantly lower in the taxol + irradiated group compared to the irradiated control group at all postirradiation time periods. A maximum decline in P N ratio was observed at 36 h postirradiation for both irradiated control and taxol + irradiated groups. The dose response for MPCE, MNCE and P N ratio was linear quadratic for both the irradiated and taxol + irradiated groups.

Effect of low doses of gamma-radiation on the steady-state spermatogenesis of mouse: a flow-cytometric study

Radiation-induced perturbations in the steady-state spermatogenesis of mouse exposed to 0.05 to 2 Gy of 60Co gamma-radiation were studied at 7 to 70 days post-irradiation flow cytometrically. Five quantifiable populations viz: elongated spermatids (HC), round spermatids (1C), spermatogonia and other diploid cells (2C), spermatogonial cells synthesizing DNA (S-phase) and primary spermatocytes (4C) were identified in the sham-irradiated controls. Exposure of mice to different doses of radiation resulted in a significant decline in the total germ-cell transformation ratio (1C:2C) at 21 and 28 days post-irradiation as compared to the control group, except for the animals exposed to 0.05 Gy. The 1C:2C ratio is sub-divided into two components viz. 4C:2C and 1C:4C. The 4C:2C ratio decreased significantly on day 14 post-irradiation, except for 0.05 Gy where it was non-significant. Consequently, meiotic transformation (1C:4C) showed a significant increase on day 14 post-irradiation compared to the sham-irradiated control barring 0.05 Gy where the difference between the two groups was non-significant. The ratio of HC:1C (cell transformation during spermiogenesis) increased significantly at day 21 post-irradiation 0.2 to 2 Gy and between day 7 and 14 for 0.05 Gy as compared to the control group. It appears that a dose as low as 0.05 Gy radiation was able to cause the perturbations in the steady-state spermatogenesis of mouse and normalcy was not restored even up to 70 days post-irradiation at all exposure doses.

Modification of radioresponse of sublethally irradiated mouse jejunum by misonidazole.

The radiation-induced changes in a critically radiosensitive tissue, jejunum of BALB/c mice and their modification by a hypoxic cell sensitizer, misonidazole (MISO), were studied. Adult mice were exposed to 1.5, 3.0 and 5.0 Gy of 60Co gamma radiation 30 min after MISO injection and quantitative studies in jejunal cross sections were carried out at different post-treatment times from 3 h to 28 d. Radiation-induced damage to the jejunal mucosa was dose-dependent and reached a maximum on day 1 post-treatment in all the groups. MISO pretreated animals did not exhibit any change in the crypt survival or crypt and villous cellularity compared to the radiation alone group. However, there was a significant suppression of mitotic activity by MISO at early intervals after irradiation. This reduction in mitosis in the drug pretreated animals appeared to affect the rate of recovery from radiation damage, which was slower and prolonged compared with that in the radiation alone group.

Quinolone Therapy in the Prevention of Mortality after Irradiation

The effect of oral therapy with three quinolones (ofloxacin, ciprofloxacin, and pefloxacin) in the prevention of postirradiation bacteremia and mortality was tested in B6D2F1 mice given 9.5 Gy 60Co gamma radiation. Only 8 of 60 (13%) untreated mice survived for 30 days, compared to 47 of 60 (78%) mice treated with ofloxacin, 44 of 60 (74%) mice treated with ciprofloxacin, and 42 of 60 (70%) mice treated with pefloxacin (P less than 0.05). The organisms recovered from the mice were Streptococcus spp. and Enterobacteriaceae. More Enterobacteriaceae were recovered from the livers of untreated animals than from the mice treated with the quinolones. However, no reduction in the number of Streptococcus spp. was noted in the animals given quinolones when compared to controls. This study shows that quinolones prolonged survival and decreased systemic spread of Enterobacteriaceae up to 30 days after exposure of mice to lethal irradiation.

Influence of Chloroquine and Lidocaine on Retention and Cytotoxic Effects of [131I]EGF: Studies on Cultured Glioma Cells

Targeting of toxic substances to the epidermal growth factor, EGF, receptor might be an attractive therapeutic approach because of the increased receptor-expression in some human tumours such as, for example, malignant gliomas and squamous lung carcinomas. Radiation effects of [131I]EGF on human malignant glioma cells growing as monolayers were analysed in this study. The cells were, in all cases, incubated for 25 min with about 350 kBq/ml [131I]EGF, which gave a total binding of 3.2-3.5 kBq/10(5) cells. The rapid release of activity from the cells caused by the normal degradation of EGF was inhibited by incubation with 30 microM chloroquine or 5 mM lidocaine added to the cell culture medium. These substances are, at these concentrations, known to inhibit proteolytic processes in lysosomes. No effects of the inhibitors alone were observed on cell growth and clonogenic survival. Inhibition of EGF degradation by chloroquine or lidocaine resulted in a significantly prolonged association of 131I with the test cells. About 70% of the initially bound radioactivity remained in the cells giving, after 6 h, a binding of 2.1-2.5 kBq/10(5) cells. A 6 h exposure to the radiation from 131I decays, mediated mainly by specifically bound EGF, gave a survival value of about 50%. Such an effect corresponds to a treatment of 2.5 Gy 60Co gamma-radiation. This is promising considering that, when monolayers are applied, only a very small fraction of the released energy from the 131I decays is deposited in the cells. Effects from non-receptor bound [131I]EGF were analysed after presaturation of the receptors with non-radioactive EGF, and gave no or very small changes in survival.