ABSTRACT
Population genetic and ecological data may help to control invasive plants, which are considered a major threat to natural habitats. In contrast to expected bottleneck events, genetic diversity of such invasive populations may be high due to extensive propagule pressure or admixture. The ecological impact of invasive species has been broadly evaluated in the field; however, long-term studies on the fate of invasive plants are scarce. We analysed genetic diversity and structure in invasive Spiraea tomentosa populations in eastern Germany and western Poland using Amplified Fragment Length Polymorphism. Potential hybridization between co-occurring diploid Sp. tomentosa and tetraploid Sp. douglasii was investigated using Flow Cytometry. The genetic analyses were complemented by data from a 13-year vegetation study in an area invaded by these Spiraea species. We found no evidence for hybridization between Spiraea species. In populations of Sp. tomentosa both genetic diversity (He = 0.26) and genetic structure (ΦPT = 0.27) were high and comparable to other outcrossing woody plants. Low levels of clonality, presence of seedlings and new patches in sites that had been colonized over the last 13 years imply that populations spread via sexual reproduction. In all habitat types, native species diversity declined following Sp. tomentosa invasion. However, detailed aerial mapping of a forest reserve with ongoing succession revealed that Spiraea spp. populations have declined over a 10-year period. Despite its potential for dispersal and negative effects on native plant communities, invasive Spiraea populations may be controlled by increasing canopy cover in forest habitats.
Subject(s)
Rosaceae , Spiraea , Amplified Fragment Length Polymorphism Analysis , Ecosystem , Forests , Genetic Variation , Spiraea/geneticsABSTRACT
During routine vegetation health surveys in the southwest of Western Australia (SWWA), several Phytophthora isolates with affinity to Clade 6a have been recovered. In this study, all known taxa from Clade 6a, P. inundata, P. humicola, P. gemini, P. 'walnut' and P. 'personii', and the new isolates were compared based on morphology and DNA sequence data from three nuclear genes and two mitochondrial genes resulting in the description of five new species, P. balyanboodja, P. condilina, P. cooljarloo, P. kwongonina and P. pseudorosacearum. With the exception of P. gemini and P. humicola, all species from Clade 6a have been recovered from natural ecosystems in SWWA. These species are morphologically similar, with predominantly ovoid sporangia and nested and extended internal proliferation. If oospores are present, they tend to be aplerotic with paragynous antheridia mostly attached adjacent to the oogonial stalk. They can all grow at 35 °C and have a fast growth rate on most agar media. These species have all been recovered from the rhizosphere soil and dead and dying plants within dry kwongon heathlands, often from water gaining sites and frequently from very isolated areas. The radiation, origin and potential ecological role of these species are discussed.
ABSTRACT
The plant hormone ethylene affects myriad developmental processes ranging from seed germination to organ senescence, and plays a crucial role in plant resistance to environmental stresses. The C-repeat/dehydration-responsive element binding factor genes (CBF1-3) are transcriptional activators involved in plant low-temperatures responses; their overexpression enhances frost tolerance, but also has various pleiotropic effects on growth and development, mainly growth retardation and delay of flowering and senescence. We found that overexpression of CBF2 in Arabidopsis suppressed leaf tissue responsiveness to ethylene as compared with wild-type plants, as manifested in significantly delayed senescence and chlorophyll degradation. In wild-type plants, exposure to ethylene at 0.1 microl.l(-1) for 48 h caused 50% reduction in chlorophyll levels as compared to leaves held in air alone, whereas CBF2-overexpressing plants required an ethylene concentration of 10.0 microl.l(-1) to cause the same effect. Furthermore, continuous exposure to ethylene at 1.0 microl.l(-1) reduced chlorophyll content in wild-type leaves by 50% after 42 h but took 72 h in CBF2-overexpressing plants. Transcript profiling of ethylene receptors and signal transduction genes in leaves of wild-type and CBF2-overexpressing plants, by means of the Affymetrix ATH1 genome array, revealed only minor differences in gene expression patterns - insufficient to explain the observed responsiveness differences. Nevertheless, we found that overexpression of CBF2 significantly increased transcript levels of 17 ABA biosynthetic and responsive genes and, thus, may have affected leaf responsiveness to ethylene via contrasting interactions with other hormones, mainly ABA. Overall, the current findings suggest that overexpression of the CBF2 transcriptional activator in Arabidopsis may, at least in part, contribute to the observed delay of leaf senescence and enhanced plant fitness by suppressing leaf responsiveness to stress-regulated ethylene.
Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/genetics , Ethylenes/pharmacology , Plant Growth Regulators/pharmacology , Plant Leaves/growth & development , Trans-Activators/metabolism , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Chlorophyll/analysis , Gene Expression Profiling , Gene Expression Regulation, Plant , Hypocotyl/growth & development , Plant Leaves/metabolism , RNA, Plant/genetics , Stress, Physiological , Trans-Activators/geneticsABSTRACT
The neoplastic transformation of human hybrid CGL1 cells is affected by perturbations from external influences such as serum batch and concentration, the number of medium changes during the 21-day expression period and cell seeding density. Nevertheless, for doses up to 1.5 Gy, published transformation frequencies for low linear energy transfer (LET) radiations (gamma-rays, MeV electrons or photons) are in good agreement, whereas for higher doses larger variations are reported. The (60)Co gamma-ray data here for doses up to 1.5 Gy, using a low-yield serum batch and only one medium change, are in agreement with published frequencies of neoplastic transformation of human hybrid cells. For 3.4 MeV alpha-particles (LET = 124 keV/mum) and 0.565 MeV monoenergetic neutrons relative to low doses of (60)Co gamma-rays, a maximum relative biological effectiveness (RBE(M)) of 2.8 +/- 0.2 and 1.5 +/- 0.2, respectively, was calculated. Surprisingly, at higher doses of (60)Co gamma-rays lower frequencies of neoplastic transformation were observed. This non-monotonic dose relationship for neoplastic transformation by (60)Co gamma-rays is likely due to the lack of a G2/M arrest observed at low doses resulting in higher transformation frequencies per dose, whereas the lower frequencies per dose observed for higher doses are likely related to the induction of a G2/M arrest.
Subject(s)
Cell Culture Techniques/methods , Cell Transformation, Neoplastic/pathology , Cell Transformation, Neoplastic/radiation effects , Cobalt Radioisotopes , Hybrid Cells/pathology , Hybrid Cells/radiation effects , Dose-Response Relationship, Radiation , Gamma Rays , HeLa Cells , Humans , Neutrons , Radiation Dosage , Relative Biological EffectivenessABSTRACT
The hybrid cell line CGL1 is the only cell line which allows quantitation of neoplastic transformation in human cells. Hybrid cells were exposed to 3.4 MeV alpha particles or to mammography X rays (29 kV(p)) and both survival and neoplastic cell transformation were assayed. For comparison, previously published data obtained with 200 kV(p) X rays are also included. Alpha particles were significantly more efficient than 29 kV(p) X rays in cell killing. Surprisingly, the efficiency of mammography X rays for the induction of neoplastic cell transformation was close to that observed for alpha particles.
Subject(s)
Alpha Particles , Cell Survival/radiation effects , Cell Transformation, Neoplastic/pathology , Cell Transformation, Neoplastic/radiation effects , Hybridomas/pathology , Hybridomas/radiation effects , Mammography , Cell Line , Dose-Response Relationship, Radiation , HeLa Cells , Humans , Radiation Dosage , X-RaysABSTRACT
PURPOSE: To measure the mutagenic effectiveness of low-filtered 30 kVp X-rays, mammography X-rays and conventional (200 kVp) X-rays in mammalian cells. MATERIALS AND METHODS: Two different cell lines and mutation assays were used. Exponentially growing SV40-transformed human fibroblasts were exposed to graded doses of mammography (29 kVp, tungsten anode, 50 microm Rh filter) or conventional X-rays and the frequency of 6-thioguanine-resistent HPRT-deficient mutants was determined. Exponentially growing hamster A(L) cells, which contain a single human chromosome 11 conferring the expression of the human surface protein CD59, were subjected to magnetic cell separation (MACS) in order to remove spontaneous mutants before irradiation with low-filtered 30 kVp (tungsten anode, 0.5 mm Al filter) or conventional X-rays. Fractions of radiation-induced CD59- mutants were quantified by flow-cytometry after immunofluorescence labelling of CD59 proteins. RESULTS: Mammography X-rays were more effective than conventional X-rays at inducing killing of human fibroblasts, whereas 30 kVp X-rays and conventional X-rays were about equally effective at killing Al. cells. Mutant frequencies were linearly related to dose in both mutation assays. An RBE = 2.7 was calculated for the yield of HPRT mutants in human fibroblasts exposed to mammography relative to conventional X-rays and an RBE = 2.4 was obtained for the CD59 mutant frequency in A(L) cells irradiated with low-filtered 30 kVp relative to conventional X-rays. CONCLUSIONS: Both low-filtered 30 kVp and mammography X-rays are mutagenic in mammalian cells in vitro. It is unknown if and how the enhanced mutagenicity of mammography X-rays measured in human cells in vitro translates into breast cancer risk for predisposed women with an enhanced inherited risk for breast cancer. Although the ICRP guidelines attribute the same relative biological effectiveness to all radiations of low LET, including X- and gamma-radiations of all energies for radiobiological protection purposes including the assessment of risks in general terms, they also state that 'for the estimation of the likely consequences of an exposure of a known population, it will sometimes be better to use absorbed dose and specific data relating to the relative biological effectiveness of the radiations concerned and the probability coefficients relating to the exposed population' (ICRP 1991: 32). This latter statement may apply for the population of familial predisposed women. We hope that the presented data on the enhanced mutagenicity of mammography X-rays may stimulate a re-evaluation of the risk assessment of mammography for familial predisposed women. In the meantime, one should be cautious and avoid early and frequent mammography exposure of predisposed women. Alternative examination methods should be applied for these women with an inherited increased risk for breast cancer.
Subject(s)
Mammography/adverse effects , Mutation , Animals , CHO Cells , Cell Line, Transformed , Cell Survival/radiation effects , Cricetinae , Female , Humans , Hybrid Cells , Hypoxanthine Phosphoribosyltransferase/genetics , Male , Mutagenicity Tests , X-Rays/adverse effectsABSTRACT
Mutation induction in the HPRT gene of human fibroblasts after irradiation with mammography-like 29 kVp or 200 kVp x-rays shows radiohypersensitivity for doses smaller than approximately 0.5 Gy. Similarly, mutation induction in the CD 59 gene on human chromosome 11 in A(L) cells shows radiohypersensitivity for doses smaller than approximately 0.5 Gy after exposure to 200 kVp x-rays, but not after irradiation with low-filtered 30 kVp x-rays. The RBE values of 29 and 30 kVp x-rays relative to 200 kVp x-rays are strongly dose dependent. For neoplastic transformation of human hybrid (CGL1) cells after irradiation with 29 or 200 kVp x-rays or 60Co gamma rays a linear-quadratic dose relationship was observed with RBE values of approximately four and eight for mammography relative to 200 kVp x-rays and 60Co gamma rays, respectively.
Subject(s)
Cell Transformation, Neoplastic/radiation effects , Mutation/radiation effects , Animals , CD59 Antigens/genetics , Cell Line, Transformed , Dose-Response Relationship, Radiation , Fibroblasts/radiation effects , Gamma Rays , Humans , Hybrid Cells , Hypoxanthine Phosphoribosyltransferase/genetics , Radiation Dosage , Relative Biological Effectiveness , X-RaysABSTRACT
The fundamental assumption implicit in the use of the atomic bomb survivor data to derive risk estimates for occupational and medical exposures is that the gamma rays of Hiroshima and Nagasaki are considered as equal efficiencies to other low LET radiations up to an LET of 10 keV.micron-1. For breast cancer induction, neoplastic cell transformation, mutation, reciprocal translocations and dicentrics in human lymphocytes, a strong and very similar dependence of the RBE values on photon energy or on LET is observed. Experimental data on mutation induction and neoplastic cell transformation in human cells show that 29 kVp X rays are by a factor of 4 and 3.4, respectively, more effective compared with 200 kVp X rays. These data are in excellent agreement with the data in the literature.
Subject(s)
Cell Transformation, Neoplastic/radiation effects , Mutagenesis , Dose-Response Relationship, Radiation , Gene Expression Regulation, Enzymologic/radiation effects , Humans , Hypoxanthine Phosphoribosyltransferase/genetics , Japan , Linear Energy Transfer , Nuclear Warfare , Survivors , X-RaysABSTRACT
The fundamental assumption implicit in the use of the atomic bomb survivor data to derive risk estimates is that the gamma rays of Hiroshima and Nagasaki are considered to have biological efficiencies equal to those of other low-LET radiations up to 10 keV/microm, including mammography X rays. Microdosimetric and radiobiological data contradict this assumption. It is therefore of scientific and public interest to evaluate the efficiency of mammography X rays (25-30 kVp) to induce cancer. In this study, the efficiency of mammography X rays relative to 200 kVp X rays to induce neoplastic cell transformation was evaluated using cells of a human hybrid cell line (CGL1). For both radiations, a linear-quadratic dose-effect relationship was observed for neoplastic transformation of CGL1 cells; there was a strong linear component for the 29 kVp X rays. The RBE(M) of mammography X rays relative to 200 kVp X rays was determined to be about 4 for doses < or = 0.5 Gy. A comparison of the electron fluences for both X rays provides strong evidence that electrons with energies of < or = 15 keV can induce neoplastic transformation of CGL1 cells. Both the data available in the literature and the results of the present study strongly suggest an increase of RBE(M) for carcinogenesis in animals, neoplastic cell transformation, and clastogenic effects with decreasing photon energy or increasing LET to an RBE(M) approximately 8 for mammography X rays relative to 60Co gamma rays.
Subject(s)
Breast Neoplasms/etiology , Cell Transformation, Neoplastic/radiation effects , Hybrid Cells/radiation effects , Linear Energy Transfer , Mammography/adverse effects , Neoplasms, Radiation-Induced/etiology , Photons/adverse effects , X-Rays/adverse effects , Animals , Breast Neoplasms/epidemiology , Cobalt Radioisotopes , Dose-Response Relationship, Radiation , Electrons/adverse effects , Female , Fibroblasts/radiation effects , HeLa Cells/radiation effects , Humans , Models, Biological , Neoplasms, Radiation-Induced/epidemiology , Nuclear Warfare , Relative Biological Effectiveness , Risk Assessment , Tumor Stem Cell AssayABSTRACT
Induction of DNA double-strand breaks (dsb) and their distribution are dependent on the energy deposition pattern within the cell nucleus (physical structure) and the ultrastructure of the chromosomes and its variation by the cell cycle and gene activities (biological structure). For electron radiation very similar RBE-values are observed for mammalian and yeast cells (AlK, 1.5 keV, 15 keV/micrometer: 2.6 in mammalian cells and 2.2 in yeast; CK 0.278 keV, 23 keV/micrometer: approx. 2.5 in mammalian cells and 3.8 in yeast). In contrast, the RBE-values for the induction of dsb of 4He2+ and light ions in the LET range from about 100 keV/micrometer up to 1000 keV/micrometer are significantly higher for yeast cells compared to mammalian cells. For example, the RBE-value of alpha-particles (120 keV/micrometer) is about 1.2 for mammalian cells whereas for yeast the RBE-value is about 2.5. The yeast chromatin has less condensed fibres compared with mammalian cells. Since a single CK photoelectron can induce only one dsb, the different condensation of the mammalian and yeast chromatin has no influence. However, particles may induce more than one dsb when traversing a chromatin fibre. The probability for the induction of closely neighboured dsb is higher the more condensed the chromatin fibres are. Since small DNA fragments (50 bp up to several kbp) are lost by standard methods of lysis, the underestimation of dsb yields increases with fibre condensation, which is in accordance with the observes dsb yields in mammalian cells and yeast. In order to obtain relevant yields of dsb (and corresponding RBE-values) the measurement of all DNA fragments down to about 50 bp are needed.
Subject(s)
DNA Damage , Fibroblasts/radiation effects , Photons , Protons , Saccharomyces cerevisiae/radiation effects , Electrons , Helium , Humans , Linear Energy Transfer , Particle Accelerators , Relative Biological Effectiveness , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/genetics , Skin/cytologyABSTRACT
Yields of DNA double-strand breaks were determined in primary human skin fibroblasts exposed to 1H and 4He ions at various linear energy transfers (LETs) and to 15 MeV electrons as the reference radiation. The values obtained for the relative biological effectiveness (RBE) were 2.03, 1.45 and 1.36 for 1H ions at LETs of 35, 23 and 7.9 keV/microm, respectively, and 1.2, 1.18, 1.38 and 1.31 for 4He ions at LETs of 124, 76, 35 and 27 keV/microm, respectively. The data were obtained using pulsed-field gel electrophoresis of DNA released from cells using the chromosomes of the yeast Saccharomyces cerevisiae as length markers and fitting the experimental mass distributions of fragmented DNA to those obtained by computer simulation of the random breakage of human chromosomes. The RBE values for induction of DSBs in mammalian cells cannot be fitted to a common RBE-LET relationship for electrons and 1H, 4He and light ions. Comparison of the RBEs for mammalian cells with the corresponding RBEs obtained for yeast cells shows similar RBEs of electrons for yeast and mammalian cells; however, for 4He and light ions in the LET range of 100 to 1000 keV/microm, the RBEs for yeast are significantly higher compared with mammalian cells. These characteristics of the RBE-LET relationships for yeast and mammalian cells are attributed to the fraction of small DNA fragments induced by particles when traversing the higher-order chromatin structures which are different to some extent in these two cell types.
Subject(s)
DNA Damage , DNA/radiation effects , Electrons , Electrophoresis, Gel, Pulsed-Field , Fibroblasts/radiation effects , Helium , Humans , Linear Energy Transfer , Relative Biological Effectiveness , Skin/radiation effectsSubject(s)
Automobile Driving , Accidents, Traffic , Aged , Aged, 80 and over , Aging/physiology , Chronic Disease , Consciousness Disorders/physiopathology , Dementia/physiopathology , Drug Therapy , Health Status , Heart Diseases/physiopathology , Humans , Physician-Patient Relations , Psychomotor Performance , Risk Factors , Vision Disorders/physiopathologyABSTRACT
For the assessment of radiation risk at low doses, it is presumed that the shape of the low-dose-response curve in humans for cancer induction is linear. Epidemiological data alone are unlikely to ever have the statistical power needed to confirm this assumption. Another approach is to use oncogenic transformation in vitro as a surrogate for carcinogenesis in vivo. In mid-1990, six European laboratories initiated such an approach using C3H 10T1/2 mouse cells. Rigid standardisation procedures were established followed by collaborative measurements of transformation down to absorbed doses of 0.25 Gy of x-radiation resulting in a total of 759 transformed foci. The results clearly support a linear dose-response relationship for cell transformation in vitro with no evidence for a threshold dose or for an enhanced, supralinear response at doses approximately 200-300 mGy. For radiological protection this represents a large dose, and the limitations of this approach are apparent. Only by understanding the fundamental mechanisms involved in radiation carcinogenesis will further knowledge concerning the effects of low doses become available. These results will, however, help validate new biologically based models of radiation cancer risk thus providing increased confidence in the estimation of cancer risk at low doses.
Subject(s)
Cell Transformation, Neoplastic/radiation effects , Neoplasms, Radiation-Induced , Radiation Protection , Animals , Biological Assay/standards , Dose-Response Relationship, Radiation , Europe , Humans , Mice , Mice, Inbred C3H , Risk AssessmentABSTRACT
The seroprevalence of human herpesvirus 8 (HHV-8) in the Swiss population was investigated. By enzyme-linked immunosorbent assay, sera reactive to the recombinant HHV-8 antigen orf 65.2 were found in 24% of human immunodeficiency virus (HIV)-positive patients without and in 92% of HIV-positive patients with Kaposi's sarcoma. Surprisingly, 20% of homosexual HIV-negative men, versus only 7% of heterosexual HIV-negative individuals and 5% of blood donors, had antibodies to HHV-8.
Subject(s)
Antibodies, Viral/blood , Herpesviridae Infections/epidemiology , Herpesvirus 8, Human/immunology , Homosexuality, Male , AIDS-Related Opportunistic Infections/epidemiology , Adult , Aged , Antigens, Viral/immunology , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Female , HIV Seronegativity , Humans , Male , Middle Aged , Prevalence , Sarcoma, Kaposi/epidemiology , Sarcoma, Kaposi/immunology , Switzerland/epidemiologyABSTRACT
BACKGROUND: With the aim of decreasing the incidence of restenosis after coronary balloon angioplasty, we developed a technique of intracoronary beta-irradiation using an endoluminally centered pure metallic 90Y source. The purpose of the present study was to evaluate the clinical feasibility and safety profile of this approach with a dose of 18 Gy delivered to the inner arterial surface. METHODS AND RESULTS: Between June 21 and November 15, 1995, fifteen patients (6 women and 9 men; mean age, 71 +/- 5 years) underwent intracoronary beta-irradiation immediately after a conventional percutaneous transluminal coronary angioplasty (PTCA) procedure. The PTCA/irradiation procedure was technically feasible in all attempted cases, and the delivery of the 18 Gy dose was accomplished without complications. In 4 patients, the intervention was completed through intra-arterial stent implantation because of dissection induced by the initial PTCA. During the follow-up period of 178 +/- 17 days (range, 150 to 225 days), no complication occurred that could be attributed to radiation therapy. No aneurysm or angiographically detectable thrombus was observed in any of the irradiated arterial segments. The clinical event rate (4 of 15 patients underwent further target lesion revascularization) and the angiographic follow-up (6 of 15 patients had a > 50%-diameter stenosis at the previously treated site) did not suggest a marked impact on the expected restenosis rate. CONCLUSIONS: This early experience demonstrates that our approach is feasible, and no side effects attributable to radiation were noted during a 6-month period of follow-up. Whether higher doses of beta-irradiation will favorably affect post-PTCA restenosis in patients must await further evaluation.
Subject(s)
Angioplasty, Balloon, Coronary , Beta Particles , Brachytherapy , Coronary Disease/therapy , Stents , Aged , Aged, 80 and over , Angina Pectoris , Brachytherapy/instrumentation , Brachytherapy/methods , Combined Modality Therapy , Coronary Disease/radiotherapy , Female , Follow-Up Studies , Humans , Male , Recurrence , Time Factors , Yttrium RadioisotopesABSTRACT
PURPOSE: A dosimetric evaluation of a new device dedicated to intravascular irradiation, associating a beta source and a centering device, was carried out before initiation of a clinical pilot study. METHODS AND MATERIALS: A 29-mm-long 90Y coil, coated with titanium and fixed to the end of a thrust wire, was introduced into the inner lumen of purpose-built centering balloons of different diameters (2.5, 3, 3.5, and 4 mm). Dose homogeneity was evaluated by studying both axial and circumferential dose variations, based on readings from thermoluminescent dosimeters (TLDs) placed on the balloon surface. Axial homogeneity was determined by comparing the readout values of dosimeters located on peripheral balloon segments with those located on segments adjacent to the midpoint of the source. The centering ability of the device was studied by comparing measurements on opposing surfaces of the balloon. The dose attenuation by water and contrast medium was evaluated and compared with that in air. The balloon contamination was studied using a contamination counter. The total 90Y coil activity was measured by liquid scintillation to relate activity to surface dose. RESULTS: Activity-surface dose correlation showed that for a linear coil activity of 1 mCi/mm, the mean dose rate at the surface of a 2.5-mm balloon filled with contrast medium was 8.29 Gy/min. The doses at the surface of larger balloons (3, 3.5, and 4 mm) filled with contrast were 78%, 59%, and 47%, respectively, of the dose measured at the surface of the 2.5-mm balloon. The coefficient of variation (CV) in surface dose for 2.5-, 3-, 3.5-, and 4-mm centering devices filled with contrast medium were 9%, 8%, 9%, and 12%, respectively. There was no statistically significant difference between readouts from central and peripheral balloon segments or among rows of dosimeters facing each other. For a 2.5-mm balloon, compared with air the dose attenuation by water and contrast medium was similar (0.70 and 0.69, respectively), but a significant difference was seen between the readouts of water- and contrast-filled balloons when the diameter was larger than 3 mm (p < 0.001). No contamination was found in the balloon shaft after source retrieval. CONCLUSION: The dosimetric tests showed very good surface dose homogeneity, demonstrating satisfactory centering of the source within the centering balloons. The achievable dose rates will permit intravascular irradiation within a short time interval. The absence of residual balloon contamination after source retrieval meets the requirements for a sealed source used in a clinical setting.
Subject(s)
Brachytherapy/methods , Coronary Disease/radiotherapy , Radiotherapy Dosage , Stents , Yttrium Radioisotopes/administration & dosage , Humans , RecurrenceABSTRACT
Overhauser effects and hence internuclear distances can be measured accurately with selective experiments designed to suppress spin diffusion. It is essential to consider effects of both transverse and longitudinal relaxation during selective radiofrequency pulses. Fitting procedures allow one to refine selected cross-relaxation rate constants, and hence determine internuclear distances with improved accuracy. For the sake of illustration, selected cross-relaxation rates are determined that correspond to short- and long-range distances involving two diastereotopic sugar protons in a double-stranded B-DNA dodecamer. Such distances are difficult to distinguish by traditional Overhauser methods because of spin-diffusion effects.
ABSTRACT
Oncogenic transformation and inactivation were investigated in C3H10T1/2 mouse embryo fibroblasts exposed to proton-induced 0.28 keV carbon K (CK)-characteristic X-rays and 60Co gamma-rays as reference radiation at high dose-rate (2-3 and 0.7 Gy/min respectively). Both oncogenic cell transformation and cell inactivation followed a linear-quadratic relationship with dose. At low doses where the linear component dominates CK ultrasoft X-rays were more effective, by a factor of 4, at inducing oncogenic cell transformation and cell inactivation compared with 60Co gamma-rays. For both endpoints the RBE of CK ultrasoft X-rays gradually decreased with increasing dose mainly due to the greater quadratic component for 60Co gamma-rays compared with CK ultrasoft X-rays. Our experimental data are in agreement with the hypothesis that single DNA double-strand breaks (dsbs), which are induced by 0.28-keV ultrasoft CK X-rays, may lead to oncogenic cell transformation. With increasing absorbed dose, i.e. with decreasing mean distance between dsbs induced by 0.28-keV ultrasoft X-rays, oncogenic cell transformation and cell inactivation may also be induced by interaction between those dsbs.
Subject(s)
Cell Transformation, Neoplastic/radiation effects , Animals , Cell Survival/radiation effects , Cells, Cultured , Dose-Response Relationship, Radiation , Gamma Rays , Mice , Mice, Inbred C3H , X-RaysABSTRACT
PURPOSE: Irradiation has been shown to be effective in preventing restenosis after dilatation in human peripheral arteries. We have developed a dedicated system for coronary intraarterial irradiation using a 90Y pure beta-emitting source inside a specially modified angioplasty balloon. This paper presents a preliminary dosimetric evaluation of this system. METHODS AND MATERIALS: Specially fabricated titanium-covered and activated yttrium wires (outer diameter 0.32 mm) were used for these studies. Dosimetry was performed using small thermoluminescent dosimeters (TLDs) placed on the surface of the 2-cm long angioplasty balloons, inflated with contrast medium to a diameter of 2.5, 3, 3.5, and 4 mm. Radioactive 90Y wires were left in the inner balloon catheter and the surface dose rate was measured and extrapolated to 72 h after activation to allow a comparison between the values obtained. After observing the poor centering of the source within the standard angioplasty balloon, a new centering balloon was developed. A conventional balloon was subdivided into four evenly spaced interconnecting chambers, thus assuring adequate centering of the inner catheter. Thermoluminescent dosimetric measurements were performed with a 3.5 mm centering balloon to evaluate the homogeneity of the surface doses compared to those measured with the conventional balloon. RESULTS: Thermoluminescent dosimetric measurements using the standard balloons filled with contrast medium were plotted semilogarithmically as a function of distance from the balloon surface. The logarithms of the measured doses fit a straight line as a function of depth. The doses at 1 mm and 3 mm are approximately 50 and 10% of the surface dose, respectively. Due to the poor centering of the source in the conventional balloons, the dispersion and standard deviations (SDs) of the measured surface doses increased proportionally to the balloon diameter (SDs are 1.89, 5.52, 5.79, and 6.46 Gy for 2.5, 3, 3.5, and 4 mm balloon diameters, respectively). For the 3.5 mm centering and conventional balloons the respective mean, minimum, and maximum surface doses were 8.41 Gy (min. 7.26; max. 9.46) and 7.89 Gy (min. 2.18; max. 16.06) and their standard deviations were 0.66 and 5.79 Gy, respectively. CONCLUSIONS: Conventional angioplasty balloons cannot ensure a homogeneous dose delivery to an arterial wall with an intralumenal 90Y beta source. Preliminary dosimetric results using a modified centering balloon show that it permits improved surface dose distribution (axial and circumferential homogeneity), making it suitable for clinical applications.
Subject(s)
Angioplasty, Balloon, Coronary/methods , Brachytherapy/methods , Yttrium Radioisotopes/therapeutic use , Angioplasty, Balloon, Coronary/instrumentation , Brachytherapy/instrumentation , Equipment Design , Radiotherapy Dosage , RecurrenceABSTRACT
The kinetics of recombinational repair of plasmid DNA double-strand breaks (dsb) and gaps (dsg) of different sizes and ends were studied. For this purpose we used the mutant rad54-3 of the yeast Saccharomyces cerevisiae, which is temperature dependent with respect to genetic recombination and rejoining of dsb/dsg, allowing us to stop these processes by shifting cells to the restrictive temperature. We found that the kinetics of repair of cohesive-ended dsb and small gaps (up to 400 bp) are similar and characterized by two phases separated by a plateau. In contrast, large gap (1.4 kbp) repair proceeds with different kinetics exhibiting only the second phase. We also investigated the repair kinetics of 400 bp gaps introduced into plasmid DNA with and without homology to chromosomal DNA allowing recombinational repair and non-recombinational repair (ligation), respectively. We found that gaps introduced in plasmid sequences homologous to chromosomal DNA are rapidly repaired by recombination. In contrast, recircularization of the gapped plasmid by ligation is as slow and inefficient as ligation of a cohesive-ended dsb. The kinetics of repair of gapped plasmids may be explained by assuming a constitutive level of enzymes responsible for the first phase of recombinational repair, while inducible enzymes, which become available at the end of the plateau, carry out the second phase of repair.