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Biomedical subjects

C A Tobias

Publications and source records attributed to C A Tobias.

At least 19 recordsLinked to original sources
PubMed2003

Delayed grafting of BDNF and NT-3 producing fibroblasts into the injured spinal cord stimulates sprouting, partially rescues axotomized red nucleus neurons from loss and atrophy, and provides limited regeneration.

Ex vivo gene therapy, utilizing modified fibroblasts that deliver BDNF or NT-3 to the acutely injured spinal cord, has been shown to elicit regeneration and recovery of function in the adult rat. Delayed grafting into the injured spinal cord is of great clinical interest as a model for treatment of chronic injury but may pose additional obstacles that are not present after acute injury, such as the need to remove an established scar, increased retrograde cell loss and/or atrophy, and diminished capacity for regeneration by neurons which may be doubly injured. The purpose of the present study was to determine if delayed grafting of neurotrophin secreting fibroblasts would have anatomical effects similar to those seen in acute grafting models. We grafted a mixture of BDNF and NT-3 producing fibroblasts or control fibroblasts into a complete unilateral cervical hemisection after a 6-week delay. Fourteen weeks after delayed grafting we found that both the neurotrophin secreting fibroblasts and control fibroblasts survived, but that only the neurotrophin secreting grafts provided a permissive environment for host axon growth, as indicated by immunostaining for RT-97, a marker for axonal neurofilaments, GAP-43, a marker for elongating axons, CGRP, a marker for dorsal root axons, and 5-HT, a marker for raphe spinal axons, within the graft. Anterograde tracing of the uninjured vestibulospinal tract showed growth into neurotrophin producing transplants but not into control grafts, while anterograde tracing of the axotomized rubrospinal tract showed a small number of regenerating axons within the genetically modified grafts, but none in control grafts. The neurotrophin expressing grafts, but not the control grafts, significantly reduced retrograde degeneration and atrophy in the injured red nucleus. Grafts of BDNF + NT-3 expressing fibroblasts delayed 6 weeks after injury therefore elicit growth from intact segmental and descending spinal tracts, stimulate modest regenerative growth by rubrospinal axons, and partially rescue axotomized supraspinal neurons and protect them from atrophy. The regeneration of rubrospinal axons into delayed transplants was much less than has been observed when similar transplants were placed acutely into a lateral funiculus or, after a 4-week delay, into a hemisection lesion. This suggests that the regenerative capacity of chronically injured red nucleus neurons was markedly diminished. The increased GAP43 reactivity in the corticospinal tracts ipsilaterally and contralaterally to the combination grafts suggests that these axons remain responsive to the neurotrophins, that the neurotrophins may stimulate both regenerative and sprouting responses, and that the grafted cells continue to secrete the neurotrophins.

Animals↗
PubMed2003

Delayed transplantation of fibroblasts genetically modified to secrete BDNF and NT-3 into a spinal cord injury site is associated with limited recovery of function.

Delivery of neurotrophic factors in acute models of spinal cord injury in adult rats can rescue axotomized neurons, promote axonal growth, and partially restore function. The extent to which repair and recovery of function can be achieved after chronic injury has received less attention. In the companion paper we show that transplanting fibroblasts genetically modified to produce neurotrophic factors into chronic (6-week) hemisection injuries results in sprouting, partial neuroprotection, but only limited regeneration. Here we describe functional consequences of this treatment using a series of behavioral tests. Adult rats received a complete unilateral C3/C4 hemisection and recovery from the injury was assessed over 5 weeks. At 6 weeks postoperative, the experimental group received grafts of a combination of fibroblasts modified to secrete BDNF or NT-3. The operated control groups received grafts of either gelfoam or gelfoam with fibroblasts expressing GFP into the lesion site. Behavioral recovery in the three groups was assessed over the next 10 weeks. Severe deficits with no recovery in any of the groups were observed in several tests (BBB, limb preference, narrow beam, horizontal rope test) that measure primarily motor function. Recovery was observed in the grid test, a measure of sensorimotor function, and the von Frey test, a measure of response to mechanical stimulation, but there were no differences between the operated control or experimental groups. Both groups also showed recovery from heat-induced hyperalgesia, with the experimental group exhibiting greater recovery than the operated control groups. In this test, delivery of neurotrophic factors from transplanted fibroblasts does not worsen responses to nociceptive stimuli and in fact appears to reduce hypersensitivity. Our data also demonstrate that additional damage to the spinal cord upon placement of a graft further compromises behavioral recovery for locomotor and postural function. Additional therapeutic interventions will be necessary to provide greater levels of recovery after chronic injuries.

Animals↗
PubMed2001

Grafting of encapsulated BDNF-producing fibroblasts into the injured spinal cord without immune suppression in adult rats.

Grafting of genetically modified cells that express therapeutic products is a promising strategy in spinal cord repair. We have previously grafted BDNF-producing fibroblasts (FB/BDNF) into injured spinal cord of adult rats, but survival of these cells requires a strict protocol of immune suppression with cyclosporin A (CsA). To develop a transplantation strategy without the detrimental effects of CsA, we studied the properties of FB/BDNF that were encapsulated in alginate-poly-L-ornithine, which possesses a semipermeable membrane that allows production and diffusion of a therapeutic product while protecting the cells from the host immune system. Our results show that encapsulated FB/BDNF, placed in culture, can survive, secrete bioactive BDNF and continue to grow for at least one month. Furthermore, encapsulated cells that have been stored in liquid nitrogen retain the ability to grow and express the transgene. Encapsulated FB/BDNF survive for at least one month after grafting into an adult rat cervical spinal cord injury site in the absence of immune suppression. Transgene expression decreased within two weeks after grafting but resumed when the cells were harvested and re-cultured, suggesting that soluble factors originating from the host immune response may contribute to the downregulation. In the presence of capsules that contained FB/BDNF, but not cell-free control capsules, there were many axons and dendrites at the grafting site. We conclude that alginate encapsulation of genetically modified cells may be an effective strategy for delivery of therapeutic products to the injured spinal cord and may provide a permissive environment for host axon growth in the absence of immune suppression.

Alginates↗
PubMed2000

Characterization and intraspinal grafting of EGF/bFGF-dependent neurospheres derived from embryonic rat spinal cord.

Recent advances in the isolation and characterization of neural precursor cells suggest that they have properties that would make them useful transplants for the treatment of central nervous system disorders. We demonstrate here that spinal cord cells isolated from embryonic day 14 Sprague-Dawley and Fischer 344 rats possess characteristics of precursor cells. They proliferate as undifferentiated neurospheres in the presence of EGF and bFGF and can be maintained in vitro or frozen, expanded and induced to differentiate into both neurons and glia. Exposure of these cells to serum in the absence of EGF and bFGF promotes differentiation into astrocytes; treatment with retinoic acid promotes differentiation into neurons. Spinal cord cells labeled with a nuclear dye or a recombinant adenovirus vector carrying the lacZ gene survive grafting into the injured spinal cord of immunosuppressed Sprague-Dawley rats and non-immunosuppressed Fischer 344 rats for up to 4 months following transplantation. In the presence of exogenously supplied BDNF, the grafted cells differentiate into both neurons and glia. These spinal cord cell grafts are permissive for growth by several populations of host axons, especially when combined with exogenous BDNF administration, as demonstrated by penetration into the graft of axons immunopositive for 5-HT and CGRP. Thus, precursor cells isolated from the embryonic spinal cord of rats, expanded in culture and genetically modified, are a promising type of transplant for repair of the injured spinal cord.

Animals↗
PubMed2000

Improved recombinant retroviral titers utilizing trichostatin A.

Recombinant retroviruses are a common vehicle to deliver an exogenous gene to a target cell, which makes them a useful tool in the field of gene therapy. A major drawback to using recombinant retroviruses is the low titer achieved, resulting in a limited number of target cells infected and subsequently poor expression of a transgene. In this study, we created an ecotropic producer cell line that contained recombinant mouse nerve growth factor (NGF) and the reporter gene LacZ. This cell line, termed psi 2/LIG/NGF, was treated with the drug trichostatin A, an inhibitor of histone deacetylase. At a concentration of 3 microM trichostatin A, the retroviral titer of this producer cell line was increased 34-fold relative to untreated control cells and 3.4-fold compared to the commonly used hyperacetylating compound sodium butyrate. Producer cells treated with trichostatin A also increased the number of primary rat marrow stromal cells infected 5.8-fold compared to untreated producer cells. These results offer a simple and effective solution for converting low titer producer cell clones to higher titer clones, which can be easily tested and applied.

3T3 Cells↗
PubMed1998

Tumor growth of FGF or VEGF transfected MCF-7 breast carcinoma cells correlates with density of specific microvessels independent of the transfected angiogenic factor.

We have previously shown that fibroblast growth factor (FGF)-1-, FGF-4-, or vascular endothelial growth factor (VEGF/VPF)-transfected MCF-7 breast carcinoma cells growing as tumors in nude mice are tamoxifen resistant and/or estrogen independent. These transfectants provide opportunity for study of in situ tumor-induced angiogenesis promoted by the individual angiogenic factors under growth-promoting versus growth-inhibiting hormonal conditions. In the present study, vessels in tumors harvested at varying times after tumor cell injection were immunohistochemically highlighted and vessel morphology and topography were scored on a scale of 0 to 4 by blinded observers. In tumors produced by all cell lines under all growth-promoting hormonal conditions, there was significantly increased abundance (P < 0.05) of edge-associated and intratumor microvessels, but not of stromally located microvessels, when compared with tumor nodules harvested under growth-inhibiting conditions, regardless of the identity of the angiogenic factor or the hormonal treatment. Image analysis of bromodeoxyuridine (BrdU)-labeled nuclei of tumors produced by all cell lines under all hormonal conditions harvested at early time points showed that mean labeling indices were highest for hormonal conditions that produced the most robust growth in that particular cell line, implying that a high BrdU labeling index is a predictor of future tumor growth in individual tumors. These results confirm previous studies that established the importance of neovascularization for tumor growth and provide validation for use of these cell lines to study the process of angiogenesis in vivo. Study of gene expression in endothelial cells in edge-associated or intratumor vessels using this model might reveal mechanisms important in tumor-induced angiogenesis in human breast cancer.

Animals↗
PubMed1998

Tamoxifen-resistant fibroblast growth factor-transfected MCF-7 cells are cross-resistant in vivo to the antiestrogen ICI 182,780 and two aromatase inhibitors.

Although the antiestrogen tamoxifen has been the mainstay of therapy for estrogen receptor (ER)-positive breast cancer, successful treatment of responsive tumors is often followed by the acquisition of tamoxifen resistance. Subsequently, only 30-40% of patients have a positive response to second hormonal therapies. This lack of response might be explained by mechanisms for tamoxifen resistance that sensitize ER pathways to small amounts of estrogenic activity present in tamoxifen or that bypass ER pathways completely. To elucidate one possible mechanism of tamoxifen resistance, we treated ovariectomized tumor-bearing mice injected with fibroblast growth factor (FGF)-transfected MCF-7 breast carcinoma cells with the steroidal antiestrogen ICI 182,780 or one of two aromatase inhibitors, 4-OHA or letrozole. These treatments did not slow estrogen-independent growth or prevent metastasis of tumors produced by FGF-transfected MCF-7 cells in ovariectomized nude mice. FGF-transfected cells had diminished responses to ICI 182,780 in vitro, suggesting that autocrine activity of the transfected FGF may be replacing estrogen as a mitogenic stimulus for tumor growth. ER levels in FGF transfectants were not down-regulated, and basal levels of transcripts for estrogen-induced genes or of ER-mediated transcription of estrogen response element (ERE) luciferase reporter constructs in the FGF expressing cells were not higher than parental cells, implying that altered hormonal responses are not due to down-regulation of ER or to FGF-mediated activation of ER. These studies indicate that estrogen independence may be achieved through FGF signaling pathways independent of ER pathways. If so, therapies directed at the operative mechanism might produce a therapeutic response or allow a response to a second course of antiestrogen treatment.

Androstenedione↗
PubMed1994

Chromosomal damage and repair in G1-phase Chinese hamster ovary cells exposed to charged-particle beams.

Chromosomal fragmentation was examined in G1-phase Chinese hamster ovary cells using the premature chromosome condensation (PCC) technique. The yield and distribution of chromatin breaks, the lesions revealed by PCC, were measured in cells exposed to X rays or each of nine particle beams covering a range of LET from 0.56 to 2700 keV/microns. The average number of breaks per cell was found to be linearly proportional to the fluence of high-LET neon ions (183 keV/microns). Assuming a linear response for the other beams, the level of breakage per unit dose rose from a plateau at the lowest LET values to a peak in the 100-200 keV/microns range and then declined continuously thereafter, eventually falling well below the low-LET plateau. The maximum breakage RBE was 1.5. The average number of breaks per particle traversal rose steadily from 0.006 to 11 breaks/cell as the LET increased from 0.56 to 2700 keV/microns. The breaks were distributed randomly within the cell population after low-LET irradiation, but became progressively over-dispersed with increasing LET. Rejoining of prematurely condensed chromosomes plus fragments was followed for up to 5 h for four particle beams having LET values between 0.56 and 183 keV/microns. An LET-dependent trend toward higher levels of residual fragments was observed.

Animals↗
PubMed1992

Protein synthesis modulates the biological effectiveness of the combined action of hyperthermia and high-LET radiation.

The combined effects of heavy-ion radiation and hyperthermia on the survival of CHO-SC1 cells and its temperature-sensitive (ts) mutant tsH1 cells were studied using accelerated neon ions followed by mild heating at 41.5 degrees C. The sequence of application of heat and high-LET radiation is significant to cell-killing effects. Heat applied to cells prior to irradiation with neon plateau ions (LET = 32 keV/microns) was less effective than heat applied immediately after irradiation. The ability of cells to synthesize new proteins plays a key role in this sequence-dependent thermal sensitization. When protein synthesis was shut down in tsH1 cells, the thermal enhancement of cell killing by high-LET radiation was the same regardless of the sequence. The thermal enhancement of radiation-induced cell killing was LET-dependent for the SC1 cells, but this was not clearly demonstrated in the tsH1 cells. Furthermore, the RBE of heated SC1 cells varied with LET and reached a maximum of greater than 3 at 80 keV/microns. In the absence of protein synthesis, the maximum RBE value was reduced to 2.6. These results suggest that the accumulation of cellular damage caused by exposure to densely ionizing particles with increasing LETs can be potentiated with active protein synthesis during postirradiation heat treatment.

Animals↗
PubMed1991

Heavy-charged-particle radiosurgery of the pituitary gland: clinical results of 840 patients.

Since 1954, 840 patients have been treated at Lawrence Berkeley Laboratory with stereotactic charged-particle radiosurgery of the pituitary gland. The initial 30 patients were treated with proton beams; the subsequent 810 patients were treated with helium ion beams. In the great majority of the 475 patients treated for pituitary tumors, marked and sustained biochemical and clinical improvement was observed. Variable degrees of hypopituitarism developed in about one-third of patients treated solely with radiosurgery. In the earlier years of the program, 365 patients underwent radiosurgery to treat selected systemic diseases by inducing hypopituitarism. Focal temporal lobe necrosis and cranial nerve injury occurred in about 1% of patients who were treated with doses less than 230 Gy.

Acromegaly↗
PubMed1989

Neoplastic cell transformation by high-LET radiation: molecular mechanisms.

Experimental data on molecular mechanisms are essential for understanding the bioeffects of radiation and for developing biophysical models, which can help in determining the shape of dose-response curves at very low doses, e.g., doses less than 1 cGy. Although it has been shown that ionizing radiation can cause neoplastic cell transformation directly, that high-LET heavy ions in general can be more effective than photons in transforming cells, and that the radiogenic cell transformation is a multi-step process [correction of processes], we know very little about the molecular nature of lesions important for cell transformation, the relationship between lethal and transformational damages, and the evolution of initial damages into final chromosomal aberrations which alter the growth control of cells. Using cultured mouse embryo cells (C3H10T1/2) as a model system, we have collected quantitative data on dose-response curves for heavy ions with various charges and energies. An analysis of these quantitative data suggested that two DNA breaks formed within 80 angstroms may cause cell transformation and that two DNA breaks formed within 20 angstroms may be lethal. Through studies with restriction enzymes which produce DNA damages at specific sites, we have found that DNA double strand breaks, including both blunt- and cohesive-ended breaks, can cause cell transformation in vitro. These results indicate that DNA double strand breaks can be important primary lesions for radiogenic cell transformation and that blunt-ended double strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship is similar for HGPRT gene mutation, chromosomal deletion, and cell transformation, suggesting common lesions may be involved in these radiation effects. The high RBE of high-LET radiation for cell killing and neoplastic cell transformation is most likely related to its effectiveness in producing DNA double strand breaks in mammalian cells. At present the role of oncogenes in radiation cell transformation is unclear.

Animals↗
PubMed1988

Split-dose recovery and protein synthesis in X-irradiated CHO cells.

A temperature-sensitive mutant for protein synthesis, CHO-tsH1, has been compared to the wild-type (WT) cell, CHO-SC1, in single- and split-radiation-dose schemes. When the exponentially growing mutant and the wild-type cells were treated at 40 degrees C for up to 3 h prior to split doses of X rays, survival was progressively reduced in the mutant compared to the wild type. In addition, if a 2-h split-dose scheme was used with a treatment of 40 degrees C given before the first dose, between the dose fractions and after the second dose, the recovery from sublethal damage (SLD) was almost completely inhibited in the mutant cells. These observations implied that a pool of proteins was involved in the recovery from sublethal X-ray damage. However, if molecular repair was measured in the mutant cell by the alkaline-unwinding technique under the same time and temperature schemes as those demonstrating a reduction in the recovery from SLD, no difference in the kinetics of DNA strand rejoining was observed compared to similar measurements made under conditions permitting SLD recovery. Misrepair processes may permit restoration of DNA strand integrity but not allow functional repair. Split-dose experiments were also done using cycloheximide to chemically inhibit protein synthesis. Under conditions which mimicked those used in the temperature-shift experiments both cell lines showed a reduction in the recovery from sublethal damage comparable in magnitude to that observed in the mutant cells when they were treated with 40 degrees C. Both the chemical and thermal inhibition of protein synthesis substantiate its necessity for the recovery from sublethal damage.

Animals↗
PubMed1988

Sequential exposures of mammalian cells to low- and high-LET radiations. II. As a function of cell-cycle stages.

The synergistic effects of low- and high-LET radiations were further studied with partially synchronized Chinese hamster V79 cells. Principally, nearly monoenergetic 425 MeV/u neon ions and 570 MeV/u argon ions produced near the Bragg peak were employed as the high-LET radiations and 225 kVp X rays as the low-LET counterpart. It was found that the killing effect due to damage interaction after sequential irradiations with the particle beam and X rays varies throughout the cell cycle. The greatest effect was observed in late-S phase which was most resistant to either of the radiations. The effect was quantitatively less in the G1/S border and in G2. Effects on pure mitotic cells have not been investigated in this study. For all cell stages studied, a dose of high-LET particles modified the shape of the X-ray survival curve in a way similar to the modification predicted by an appropriately selected X-ray dose. This finding suggests that the mechanism for the synergistic effects is similar to that operating for sequential treatments with X rays alone. Experiments with an S population, either incubated at 37 degrees C or room temperature between fractionation of high- and low-LET radiation treatments further verified that the damage involved is a repairable type. At a certain fractionation interval (6 to 8 h) following a dose of high-LET treatment, initially asynchronous cells were found to be very sensitive to X-irradiation. It is noteworthy that the net killing measured at this "radiosensitive window" was as effective as the killing observed by "immediately" sequential treatments with the same doses of high- and low-LET radiations. Such a time window also existed when the order of the treatment sequence was reversed except that the time of occurrence was earlier and the window was broader. This sensitization effect may be explained by radiation-induced G2 arrest together with an increase of radiosensitivity as the previously irradiated cells progress into S phase. Radiotherapy strategies using combined high-LET and low-LET radiations for rapidly proliferative tumors are presented.

Animals↗
PubMed1986

Dose protraction studies with low- and high-LET radiations on neoplastic cell transformation in vitro.

A major objective of our heavy-ion research is to understand the potential carcinogenic effects of cosmic rays and the mechanisms of radiation-induced cell transformation. During the past several years, we have studied the relative biological effectiveness of heavy ions with various atomic numbers and linear energy transfer on neoplastic cell transformation and the repair of transformation lesions induced by heavy ions in mammalian cells. All of these studies, however, were done with a high dose rate. For risk assessment, it is extremely important to have data on the low-dose-rate effect of heavy ions. Recently, with confluent cultures of the C3H10T1/2 cell line, we have initiated some studies on the low-dose-rate effect of low- and high-LET radiation on cell transformation. For low-LET photons, there was a decrease in cell killing and cell transformation frequency when cells were irradiated with fractionated doses and at low dose rate. Cultured mammalian cells can repair both subtransformation and potential transformation lesions induced by X rays. The kinetics of potential transformation damage repair is a slow one. No sparing effect, however, was found for high-LET radiation. There was an enhancement of cell transformation for low-dose-rate argon (400 MeV/u; 120 keV/micrometer) and iron particles (600 MeV/u; 200 keV/micrometer). The molecular mechanisms for the enhancement effect is unknown at present.

Animals↗
PubMed1986

The effect of space radiation of the nervous system.

The long-term effects of irradiation by accelerated heavy ions on the structure and function of the nervous system have not been studied extensively. Although the adult brain is relatively resistant to low LET radiation, cellular studies indicate that individual heavy ions can produce serious membrane lesions and multiple chromatin breaks. Capillary hemorrhages may follow high LET particle irradiation of the developing brain as high RBE effects. Evidence has been accumulating that the glial system and blood-brain barrier (BBB) are relatively sensitive to injury by ionizing radiation. While DNA repair is active in neural systems, it may be assumed that a significant portion of this molecular process is misrepair. Since the expression of cell lethality usually requires cell division, and nerve cells have an extremely low rate of division, it is possible that some of the characteristic changes of premature aging may represent a delayed effect of chromatin misrepair in brain. Altered microcirculation, decreased local metabolism, entanglement and reduction in synaptic density, premature loss of neurons, myelin degeneration, and glial proliferation are late signs of such injuries. HZE particles are very efficient in producing carcinogenic cell transformation, reaching a peak for iron particles. The promotion of viral transformation is also efficient up to an energy transfer of approximately 300 keV/micron. The RBE for carcinogenesis in nerve tissues remains unknown. On the basis of available information concerning HZE particle flux in interplanetary space, only general estimates of the magnitude of the effects of long-term spaceflight on some nervous system parameters may be constructed.

Abnormalities, Radiation-Induced↗
PubMed1985

DNA-mediated gene transfer efficiency is enhanced by ionizing and ultraviolet irradiation of rodent cells in vitro. I. Kinetics of enhancement.

The enhancement effects of ionizing and ultraviolet radiation on the efficiency of DNA-mediated gene transfer were studied. The established cell line, Rat-2, consists of cells that are density-dependent contact-inhibited and produce flat monolayers in vitro. When these cells are infected with SV40 virus, a small fraction of cells becomes morphologically "transformed" due to the stable expression of the viral A-gene. Rat-2 cells are competent for DNA-mediated gene transfer, deficient in thymidine kinase activity (TK-), and will die in HAT selective media. Confluent Rat-2 cells were transfected with purified SV40 viral DNA (via calcium phosphate precipitation), irradiated with either X rays or ultraviolet, trypsinized, plated, and assayed for the formation of foci on Rat-2 monolayers. Both ionizing and ultraviolet radiation enhanced the frequency of A-gene transformants/survivor compared to unirradiated transfected cells. These enhancements were nonlinear and dose dependent. A recombinant plasmid, pOT-TK5, was constructed that contained the SV40 virus A-gene and the Herpes Simplex virus (HSV) thymidine kinase (TK) gene. Confluent Rat-2 cells transfected with pOT-TK5 DNA and then immediately irradiated with either X rays or 330 MeV/amu argon particles at the Berkeley BEVALAC showed a higher frequency of HAT+ colonies/survivor than unirradiated transfected cells. In both cases the enhancement contained a linear and a higher order component in dose, but the argon ions were at least twice more efficient than X rays in producing enhancement per unit dose. Rat-2 cells transfected with pOT-TK5, X-irradiated, and assayed for either TK transformation or A-gene transformation showed the same dose dependence for radiation enhancement. Rat-2 cells transfected with the plasmid, pTK2, containing only the HSV TK-gene were enhanced for TK transformation by both X rays and ultraviolet radiation. SV40 A-gene products are not necessary for the radiation enhancement of the efficiency of gene transfer. This in vitro system will be used to study the lesions produced by ionizing radiation on mammalian cell DNA that may act as substrates for integration of exogenously introduced plasmid DNA.

Animals↗
PubMed1985

Heavy-ion effects on mammalian cells: inactivation measurements with different cell lines.

In track segment experiments, the inactivation of different mammalian cells by heavy charged particles between helium and uranium in the energy range between 1 and 1000 MeV/u has been measured at the heavy ion accelerator Unilac, Darmstadt, the Tandem Van de Graaf, Heidelberg, and the Bevalac, Berkeley. The inactivation cross sections calculated from the final slope of the dose-effect curves are given as a function of the particle energy and the linear energy transfer.

Animals↗