Search

Background: NEK1, the first mammalian ortholog of the fungal protein kinase never-in-mitosis A (NIMA), is involved early in the DNA damage sensing/repair pathway. A defect in DNA repair in NEK1-deficient cells is suggested by persistence of DNA double strand breaks after low dose ionizing radiation (IR). NEK1-deficient cells also fail to activate the checkpoint kinases CHK1 and CHK2, and fail to arrest properly at G1/S or G2/M-phase checkpoints after DNA damage. Results: We show here that NEK1-deficient cells suffer major errors in mitotic chromosome segregation and cytokinesis, and become aneuploid. These NEK1-deficient cells transform, acquire the ability to grow in anchorageindependent conditions, and form tumors when injected into syngeneic mice. Genomic instability is also manifest in NEK1 +/- mice, which late in life develop lymphomas with a much higher incidence than wild type littermates. Conclusion: NEK1 is required for the maintenance of genome stability by acting at multiple junctures, including control of chromosome stability.

The lethal effects of acute doses of radiation on fertility are well known. Germ cells are killed or damaged within a short time of exposure to radiation. In recent years, radiotherapy of patients with cancer has led to an increased number of sustained remissions. However, among the long-term side effects of radiation, injury to the reproductive system is of particular concern. Many papers have been reported so far on the antioxidant effect of curcumin. The present study, we hypothesized that curcumin can minimize germ-cell depleÖZGÜNtion and morphological features of late cell damage in the rat testis following X-irradiation. The animals were divided into 4 groups: the first group was the control and the other three were the experimental groups. 6 Gy X ray in a single fraction was applied into the scrotal areas of the subjects except the control and curcumin groups in order to form radiation damage. The rats in the second and forth groups were given curcumin (a dose of 100 mg/kg body weight) orally three times a week during a seven-week period, beginning the week before radiation therapy. The rats in the first and third groups received tap water in the same way. Testis biopsy samples from the all groups were taken on the 7th week. All samples were processed and observed at the light microscopic levels. In the present study, radiation exposure caused severe degenerative changes in testes. Spermatogenesis had arrested in seminiferous tubules and the majority of the tubules were found to be atrophic, absent of germ cells. It was identified that curcumin hadn't been effective in the prevention of all damages caused by radiation. [ABSTRACT FROM AUTHOR]

Whole body irradiation with a single 10-Gy dose caused increase in lipid peroxidation and a transient decrease in cellular glutathione content in rat spleen, demonstrating elevated oxidative stress. The irradiation also caused increases in activities of glutathione peroxidase (GPx), glutathione reductase (GR), and glucose 6-phosphate dehydrogenase (G6PD), the enzymes carrying out glutathione redox cycling; but not glutamate cysteine ligase (GCL), the enzyme in glutathione synthesis process. Increases in catalase (CAT) activity and heme oxygenase-1 (HO-1) and glutathione S-transferase pi (GSTpi) protein levels were also exhibited after irradiation. Administration of Se-methylselenocysteine (MSC) (0.75 mg/rat/day, for 1 week) resulted in increases in GPx, G6PD, and CAT activities and GSTpi protein level in non-irradiated spleen, without affecting glutathione and lipid peroxidation levels. The MSC pretreatment prior to irradiation abrogated the irradiation-induced increase in lipid peroxidation, and it induced increases in glutathione content, GCL, GPx and CAT activities, and HO-1, GSTpi, and peroxiredoxin 2 protein levels upon irradiation. Our results suggest a role for MSC pretreatment in prevention of irradiation-induced oxidative damage in spleen by reinforcing antioxidant capacity, particularly the glutathione system. [ABSTRACT FROM AUTHOR]

Purpose: A study of irradiated (0.25-2 Gy) murine bone marrow has investigated the relationships between apoptotic responses of cells exposed in vivo and in vitro and between in vivo apoptosis and tissue cytotoxicity. Materials and methods: The time course of reduction in bone marrow cellularity in vivo was determined by femoral cell counts and apoptosis measurements obtained using three commonly used assays. Inflammatory pro-apoptotic cytokine production at 24 h post-exposure in vivo was investigated using a bystander protocol. Results: In vivo, there is a dose- and time-dependent non-linear reduction in bone marrow cellularity up to 24 h post- irradiation not directly represented by apoptosis measurements. The majority of cells are killed within 6 h but there is on-going cell loss in vivo up to 24 h post-irradiation in the absence of elevated levels of apoptosis and associated with the induction of cytokines produced in response to the initial tumor protein 53 (p53)-dependent apoptosis. Conclusion: The results demonstrate that small increases in measured apoptosis can reflect significant intramedullary cell death and with apoptotic processes being responsible for pro-inflammatory mechanisms that can contribute to additional on-going cell death. The findings demonstrate the importance of studying tissue responses when considering the mechanisms underlying the consequences of radiation exposures. [ABSTRACT FROM AUTHOR]

Abstract: A new isolate, Kocuria sp. ASB 107 from the Ab-e-Siah mineral radioactive spring (Ramsar, Mazandaran Province, Iran) was characterized on the basis of morphological and biochemical characteristics plus 16S rRNA gene sequencing. The isolate is most closely related to Kocuria rosea DSM 20447T (99.7% sequence similarity) and Kocuria polaris DSM 14382T (99.5%). This strain has some resistance to various genotoxic stresses, such as ionizing radiation, ultraviolet (256 nm- UV) and corona discharge. The 90% lethal doses (D 10) for gamma-rays and 256 nm-UV are 2 kGy and 400 J m−2, respectively, in definite cell concentration. Moreover, the resistance for a definite energy of corona discharge is 10 s, about 10 times greater than that of Escherichia coli. The growth temperature of the strain ASB 107 is 0–37 °C in TSB (tryptic soy broth). This study is the first report on the psychrotrophic radio-resistant bacteria belonging to the Kocuria genus isolated from Ab-e-Siah spring. [Copyright &y& Elsevier]

When a biological system is either accidentally or intentionally exposed to radiation, the energy absorbed triggers a number of successive events including damage to living tissues. Major radiation damage is due to the aqueous free radicals generated by the radiolysis of water. These free radicals act as molecular marauders and in turn damage DNA, mitochondrial membrane, lipid, cellular protein, resulting in cellular dysfunction and mortality. In view of the above mentioned facts an experiment was conducted to study the genotoxic effects of γ radiation and its dose effectiveness. The present experiment was conducted on samples of plasmid pBR322 DNA as the in vitro experimental model devoid of any DNA repair and replication machinery. The samples were exposed to different doses of gamma radiations from 1 to 200 Gy. Exposure of plasmid pBR322 DNA to γ radiation resulted in production of single strand breaks as a result of which, the supercoiled (SC) form was converted to relaxed form (RL). Exposure of radiation, even at very low dose of 1 Gy, exhibited a significant damage to DNA resulting in about 70% SC form and 30% RL form of DNA. At a dose of 10 Gy the SC form was reduced to about 37% and further 5% at a dose of 50 Gy with about 88.5 and 6.5% RL and linear (L) forms of DNA respectively. Thus, the disappearance of supercoiled form of plasmid pBR322 DNA was found to be directly related to radiation dose and exhibited a radiation dose dependent pattern. [ABSTRACT FROM AUTHOR]

Management of radiation-induced reactive oxygen/nitrogen species requires a holistic approach to mitigate the deleterious effects of free radicals. Flora of the Himalayas, which prevails under extreme climatic conditions, has been explored for its potential utility to develop radioprotective drugs. The Himalayan high altitude medicinal plant, Podophyllum hexandrum Royle, was selected on the basis of its unique properties, and a novel fractionated nonpolar extract (REC-2003) was prepared and evaluated for radioprotective efficacy, in vitro as well as in vivo. The free radical scavenging activity of REC-2003 was found to be > 75% (20 μg/ml) with maximum superoxide scavenging activity (57.56 ± 1.38%) recorded at 1 mg/ml concentration (tetrazolium-based estimation). More than 30% inhibition of nitric oxide radicals was observed at concentrations > 0.5 mg/ml, while hydroxyl radical scavenging activity (deoxy-D-ribose assay) exhibited a dose-dependent (100–600 μg/ml) increase. Significantly high (90%) protection to human erythrocytes was observed at 75 μg/ml, which was found to be the most optimized dose. Similarly, more than 90% inhibition was observed against lipid peroxidation (evaluated by estimating levels of malondialdehyde). The significant antihemolytic potential of REC-2003 could be attributed to its ability to scavenge free radicals, reduce peroxidative stress on lipid membranes, and render protection to DNA (evaluated using plasmid relaxation assay). All these activities holistically contributed toward the radioprotective ability. REC-2003 (8 mg/kg BW; intraperitoneal (i.p.), −30 min) rendered > 80% total-body protection in Swiss Albino Strain ‘A’ mice [against lethal radiation (10 Gy)] in a 30-day survival assay. Phytochemical characterization of the constituents of REC-2003 revealed the presence of polyphenolics (flavonoids). The characterized constituents also included the aryl-tetralin lignans like podophyllotoxin, its glycoside, 4′-demethyl derivative, and epi-podophyllotoxin. The optimized requisite single dose (8 mg/KgBW; i.p., −30 min) for obtaining significant radioprotection is reasonably low and establishes its future utility as a dietary supplement in the medical management of free radical-mediated diseases and specifically for rescue missions during nuclear and radiological emergencies (NREs). [ABSTRACT FROM AUTHOR]