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At least 19 recordsLinked to original sources
PubMed1987

Genetic effects of 5-hydroxymethyl-2'-deoxyuridine, a product of ionizing radiation.

Ionizing radiation causes formation of heterogeneous types of damage to DNA. Among those, 5-hydroxymethyl-2'-deoxyuridine (HMdU) was identified as a major thymidine derivative in gamma-irradiated HeLa cells [G.W. Teebor, K. Frenkel and M.S. Goldstein (1984) Proc. Natl. Acad. Sci. (U.S.A.), 81, 318-321]. We report here that HMdU is a strong inducer of lambda prophage in Escherichia coli WP2s(lambda) and is highy mutagenic in Salmonella typhimurium. HMdU causes his+ revertants in strains TA100, which reverts predominantly by base-pair substitution at G-C sites, and TA97, which reverts mainly by frameshift mutation at G-C sites. It does not cause reversion in TA98, another frameshift-sensitive strain, nor in strains TA1535 and TA1537. Of those tested, only the last two strains do not contain pkM101, a plasmid which enhances mutagenic effects of ionizing radiation. HMdU also causes reversion in strains TA102 and TA104, which detect oxidative damage and can revert by base-pair substitution at A-T base pairs at the hisG428 site. We show that HMdU can be incorporated into DNA of TA100 and that, in addition to causing point mutations, it causes suppressor mutations as well. The ability of HMdU to induce lambda prophage and its strong mutagenicity in Salmonella typhimurium provide evidence that the presence of HMdU in DNA is biologically significant and may play a major role in the genetic consequences of ionizing radiation and other types of oxidative damage.

Bacteriophage lambda↗
PubMed1988

The combined effects of mixtures of ionizing radiations.

Ionizing radiation is a special group of toxic agents whose general interaction can be calculated. This was demonstrated using a radiation interaction model previously published. In this paper, this model is refined and mathematically reformulated using a unified set of assumptions. It postulates the existence of a common intermediate lesion and the relative action of lesions before, at and after this common stage. General quantitative dose-effect relationships of mixed radiations can be derived from the dose-effect relationships of the components in the mixture.

Animals↗
PubMedDate not supplied

Comparison of functional and morphological deficits in the rat after gestational exposure to ionizing radiation.

Ionizing radiation is a precise tool for altering formation of the developing cerebral cortex of the fetal rat. Whole body exposure of the pregnant rat on gestational day 13, 15 or 17 to 1.0 Gy of gamma radiation resulted in maximum thinning of the cortex on days 15 and 17. In the preweaning period, functional tests (negative geotaxis, reflex suspension, continuous corridor and gait) were most affected by irradiation gestational day 15, as was body weight. When a lower dose of radiation (0.75 Gy) was used on gestational day 15, the damage to the cortex was much less but behavioral changes were still present. Frontal, parietal and occipital areas of the cortex were approximately equally affected. Using stepwise multiple regression analysis, the linkage of functional tests and cortical thickness was examined. Functional variables which were most commonly included as predictors of frontal and parietal cortex were negative geotaxis and continuous corridor. Occipital cortical layers were not predicted by behavioral variables. In predicting function using cortical variables, frontal cortex was better than parietal and occipital cortex was the poorest predictor.

Animals↗
PubMed1992

Interaction of photodynamic treatment and either hyperthermia or ionizing radiation and of ionizing radiation and hyperthermia with respect to cell killing of L929 fibroblasts, Chinese hamster ovary cells, and T24 human bladder carcinoma cells.

Both hyperthermia and photodynamic therapy of cancer are frequently used in combination with other treatment modalities in order to improve tumor control with minimal damage to normal tissues. The present results indicate that the most effective combination of treatment modalities is different in different cell types. For instance, ionizing irradiation and hyperthermia exhibited additivity when applied to L929 fibroblasts, in contrast to the synergistic interaction described before in many other cell lines. This aberrant behavior of L929 cells could be explained by the relative insensitivity of DNA repair in these cells to hyperthermia. Conversely, a synergistic interaction between photodynamic treatment and ionizing irradiation was observed with L929 fibroblasts, whereas these treatments were additive with Chinese hamster ovary and T24 cells. The synergistic interaction with L929 cells could be explained by the high sensitivity of DNA repair in these cells to photodynamic treatment. Photodynamic treatment and hyperthermia exhibited a synergistic interaction in L929, Chinese hamster ovary, and T24 cells. The critical target for cell killing by the combined treatment protocol in these cell lines has not yet been elucidated. In all three cell lines, however, analysis of the results according to the Arrhenius equation revealed a photodynamically induced change of both the frequency factor and the activation energy of subsequent thermal cell killing. It is considered that this may indicate a basic mechanism, in which a particular protein is a common, critical target of the two modalities of treatment.

Animals↗
PubMed1986

Exposure of human lymphocytes to ionizing radiation reduces mutagenesis by subsequent ionizing radiation.

The effect of prior incubation with [3H]thymidine on survival and mutagenesis after X-irradiation of human lymphocytes was studied by incubating lymphocytes with 0.001-1.0 mu Ci/ml [3H]thymidine for 6 h at 37 degrees C and then irradiating with 150 or 300 rad. Survival was measured using lymphocyte cloning and mutagenesis was measured using 6-thioguanine selection to detect clones mutated at the hypoxanthine phosphoribosyltransferase locus. [3H]Thymidine alone had no effect on survival or mutagenesis and X-radiation alone produced the expected decrease in survival and increase in mutations. [3H]Thymidine prior to X-radiation had no effect on lethality of X-radiation but at concentrations of 0.1 and 1.0 mu Ci/ml produced a significant decrease in the number of mutations induced after both 150 and 300 rad. The results suggest that ionizing radiation, produced by disintegration of 3H, reduces the mutagenic effect of a subsequent exposure to ionizing radiation by induction of a system which prevents or repairs a restricted class of radiation damage.

Cell Survival↗
PubMed1991

Biological consequences of gene regulation after ionizing radiation exposure.

Ionizing radiation is a ubiquitous environmental mutagen and carcinogen widely used in cancer therapy. However, little is known about the induction of cellular signaling events and specific gene expression after radiation exposure. We review the accumulating evidence that ionizing radiation induces signal transduction pathways involving activation of protein kinase C and a program of genetic events that may contribute to the biological effects of x rays.

Base Sequence↗
PubMed1989

Standards and calibration facilities of the Australian Radiation Laboratory for ionizing radiation beams.

The Australian Radiation Laboratory (ARL) maintains national standards of exposure and working standards of absorbed dose. Some of the exposure standards maintained by ARL have been compared recently with those of the Bureau International des Poids et Mesures (BIPM) for 100 to 250 kV x-rays and 60Co gamma rays. The absorbed dose standard for 60Co gamma rays is compared regularly with other standards through the International Atomic Energy Agency (IAEA) and World Health Organization (WHO). All results show good agreement. A range of calibration qualities is offered at ARL, extending from 10 kV x-rays to 60Co gamma rays. A system of regional facilities has been developed for radiation protection calibrations; each facility is supplied with a set of 137Cs sources and an ionization chamber and electrometer for use with x-rays. The system is now almost complete throughout Australia.

Australia↗
PubMed1992

Down-regulation of cell cycle control genes by ionizing radiation.

The cellular responses to ionizing radiation include growth arrest, DNA repair, and lethality. However, little is known about the signaling events responsible for these responses. The present studies have examined the effects of ionizing radiation on the expression of genes involved in cell cycle control. The results demonstrate that the treatment of asynchronous cells with 20 Gy ionizing radiation is associated with transient down-regulation of the cdc2, cyclin A, cyclin B, and cdc25 genes. This effect was associated with transient induction of the c-jun gene. RNA stability studies demonstrate that the down-regulation of gene expression following ionizing radiation exposure is at least in part due to a decrease in transcript half-life. Other studies were performed with elutriated cells enriched for populations in G1 and S phases. Treatment of G1 enriched cell populations with 10 Gy resulted in a selective decrease in cyclin B mRNA levels, whereas this effect on cyclin B expression was less pronounced at 5 Gy and undetectable at 1 Gy. Similar results were obtained with S phase enriched cells. Taken together with clonogenic survival studies, these findings indicate that down-regulation of cell cycle control gene expression is associated with lethality, whereas lower doses of ionizing radiation have little, if any, effect on the expression of these genes. The findings also suggest that DNA damage may activate signaling events which regulate expression of cell cycle control genes.

CDC2 Protein Kinase↗
PubMed1991

Cyclin B expression in HeLa cells during the G2 block induced by ionizing radiation.

After exposure to ionizing radiation, eukaryotic cells undergo a division delay which is reflected by increased time spent in the G2 portion of the cell cycle. Recent information identifies increased levels of mitotic cyclins as key biochemical events initiating mitosis. In HeLa cells cyclin B mRNA and protein levels have been shown to increase in G2 and to decrease after division is completed. Cyclin B protein binds to cdc2, resulting in histone kinase activity which is necessary for the initiation of mitosis. Accordingly, we chose to investigate how cyclin B mRNA and protein levels were perturbed by irradiation in order to gain further understanding of the mechanisms by which ionizing radiation leads to a division delay. Our experiments revealed at least two effects on cyclin B regulation which might contribute to the division delay: (a) when HeLa cells were irradiated in S phase, there was a delay in the accumulation of cyclin B mRNA; (b) when cells were radiated in G2 phase, at a time when mRNA levels were increasing, a division delay was induced which coincided with a markedly lowered level of cyclin B protein despite high levels of the mRNA.

Blotting, Northern↗
PubMed1972

Synergistic inactivation of viruses by heat and ionizing radiation.

Viral inactivation by heat and/or ionizing radiation is analyzed in terms of a kinetic model. The phenomenon of synergistic viral inactivation observed when viruses are exposed to the simultaneous application of heat and ionizing radiation is interpreted within the framework provided by this three-term model. Data on the inactivation of T4 bacteriophage by heat and/or ionizing radiation is presented, and the kinetic model is used to provide a description of observed dose rate and temperature dependences. Extension of the model to other viral systems inactivated by heat and ionizing radiation is considered, and the general applicability of these analyses suggests that the kinetic model may well serve as an extension of target theory in describing the radiobiological effects of ionizing radiation.

Coliphages↗
PubMed1989

Effect of metals on nucleoside hydroperoxide, a product of ionizing radiation in DNA.

Ionizing radiation causes formation of thymine hydroperoxides in DNA. Their decomposition generates more stable products and active oxygen species which may oxidize other DNA bases. We have determined the effects of free and chelated metal ions on the degradation of 5-hydroperoxymethyl-2'-deoxyuridine (HPMdU). Two products were formed as analyzed by HPLC: 5-hydroxymethyl-2'-deoxyuridine (HMdU) and 5-formyl-2'-deoxyuridine (FdU). Sn(II) and Fe(II) caused instantaneous HPMdU degradation; Sn(II) generated only HMdU, whereas Fe(II) formed about equal amounts of both. Sn(IV) and Fe(III) were inactive. Cu(I), Cu(II), and Co(II) caused a time-dependent formation of both products, with FdU predominating. In the presence of Cu(I), Cu(II), and Fe(II), formate inhibited formation of HMdU but enhanced that of FdU. EDTA abolished Cu(I)-induced decomposition of HPMdU but only decreased that which was mediated by Cu(II). In contrast, EDTA enhanced the activity of Fe(III) with a time-dependent formation of FdU. EDTA and diethylenetriaminepentaacetic acid (DTPA) caused an instantaneous Fe(II)-mediated decomposition of HPMdU to FdU. Only desferal partially inhibited the activity of Fe(II), whereas the activities of Cu(I), Cu(II), and Fe(III) were blocked by desferal and DTPA. Possible mechanisms of HPMdU degradation by metal ions in the absence or presence of formate or chelators as well as formation of the .OH are discussed.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

[Inactivation of isogenous strains of Bacillus subtilis and their mixtures by ionizing radiation].

Resistance to ionizing radiation of vegetative cells, spores and dehydrated cultures was studied with isogenous strains of Bacillus subtilis with defects in the repair systems. In vegetative cells of different classes of the recombination deficient mutants, DL90 was 31-35% of LD90 of the wild type cells. Differences in radiosensitivity of the vegetative cells were more pronounced cf. the spores and dehydrated cells: LD90 of rec- mutants was 55-88%; LD90 of uvr- mutants was 120% of LD90 of the parent bacterial cells.

Bacillus subtilis↗