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L Böhm

Publications and source records attributed to L Böhm.

At least 19 recordsLinked to original sources
PubMed1996

RBE variation between fast neutron beams as a function of energy. Intercomparison involving 7 neutrontherapy facilities.

In fast neutron therapy, the relative biological effectiveness (RBE) of a given beam varies to a large extent with the neutron energy spectrum. This spectrum depends primarily on the energy of the incident particles and on the nuclear reaction used for neutron production. However, it also depends on other factors which are specific to the local facility, eg, target, collimation system, etc. Therefore direct radiobiological intercomparisons are justified. The present paper reports the results of an intercomparison performed at seven neutrontherapy centres: Orléans, France (p(34)+Be), Riyadh, Saudi Arabia (p(26)+Be), Ghent, Belgium (d(14.5)+Be), Faure, South Africa (p(66)+Be), Detroit, USA (d(48)+Be), Nice, France (p(65)+Be) and Louvain-la-Neuve, Belgium (p(65)+Be). The selected radiobiological system was intestinal crypt regeneration in mice after single fraction irradiation. The observed RBE values (ref cobalt-60 gamma-rays) were 1.79 +/- 0.10, 1.84 +/- 0.07, 2.24 +/- 0.11, 1.55 +/- 0.04, 1.51 +/- 0.03, 1.50 +/- 0.04 and 1.52 +/- 0.04, respectively. When machine availability permitted, additional factors were studied: two vs one fraction (Ghent, Louvain-la-Neuve), dose rate (Detroit), influence of depth in phantom (Faure, Detroit, Nice, Louvain-la-Neuve). In addition, at Orléans and Ghent, RBEs were also determined for LD50 at 6 days after selective abdominal irradiation and were found to be equal to the RBEs for crypt regeneration. The radiobiological intercomparisons were always combined with direct dosimetric intercomparisons and, when possible in some centres, with microdosimetric investigations.

Abdomen↗
PubMed1996

Influence of ouabain on cell inactivation by irradiation.

BACKGROUND: It has been suggested that irradiation affects the function of the Na(+)-K(+)-ATPase. Here we examine the influence of the inhibitor ouabain on the cytotoxicity of irradiation. MATERIAL AND METHODS: Cell colony assay, cell survival, 86Rb-uptake, flow cytometry. RESULTS: In V79, HeLa and A549 cells ouabain alone causes a significant growth reduction at medium concentrations of 10(-4) M, 10(-6) M and 10(-7) M, respectively. When cells were exposed to the drug for 1 h and subsequently irradiated, the SF2 values decreased from 0.55 to 0.41, from 0.42 to 0.18 and from 0.57 to 0.35 in V79, HeLa and A549 cells, respectively. These effects were manifest at drug concentrations of 10(-3) M, 10(-6) M and 10(-7) M respectively, where Na(+)-K(+)-ATPase activity as measured by 86Rb-uptake was reduced to 40 to 60% of the control value. Addition of the drug after irradiation and when the G2/M cell cycle block was firmly established, markedly delayed the recovery of cells for well over 6 h and G1 levels remained at 50% of the control values. CONCLUSION: It is concluded that ouabain is strongly dose modifying in the human cell lines HeLa and A549 at concentrations which correlate with the inhibition of the Na(+)-K(+)-ATPase. Ouabain also inhibits the recovery of cells blocked in the cell cycle by irradiation.

Animals↗
PubMed1996

Radiosensitivity variations in human tumor cell lines exposed in vitro to p(66)/Be neutrons or 60Co gamma-rays.

BACKGROUND: Neutron therapy should be beneficial to patients with tumor types which are resistant to photons but relatively sensitive to high-LET radiation. In this work the potential therapeutic gain of a clinical neutron beam is evaluated by quantifying the variations in radiosensitivity of different cell lines to neutrons and photons. MATERIAL AND METHODS: Different cell lines were exposed in vitro to p(66)/Be neutrons or 60Co gamma-rays. Micronuclei frequencies in binucleated cells and surviving fractions were determined for each cell type. RESULTS: Following exposure to either 1 or 1.5 Gy neutrons, micronuclei frequencies were significantly correlated with that observed for 2 Gy photons. A weak but significant correlation between the variation in neutron RBE values, determined from survival curve inactivation parameters and the mean inactivation doses for photon exposures, was also established. CONCLUSION: It is concluded that although neutron and photon sensitivities are related, the use of this high energy neutron source may constitute a potential therapeutic gain for tumor types that can be identified as very resistant to photons. Considering that a definitive oxygen gain factor has been established for this neutron beam the observed therapeutic gain is expected to be further enhanced in tumors where hypoxia protects cells from conventional radiation damage.

Beryllium↗
PubMed1994

Cyclotron future.

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Cyclotrons↗
PubMed1994

Effect of pentoxifylline on radiation damage and tumor growth.

PURPOSE: Inactivation of tumor cells by photon irradiation can be markedly improved by tumor oxygenation. We have investigated the effect of the vasoactive drug pentoxifylline with respect to cell toxicity, radiation sensitivity, repair and tumor growth. METHODS: V79 and Hela cell survival curves and determination of the tumor volume using rhabdomyosarcoma growth in BALB/c mice. RESULTS: In the presence of 1 mM pentoxifylline, survival of V79 Chinese hamster lung fibroblasts and human Hela cells at a dose level of 2 Gy is reduced by factors of 1.12 +/- 0.09 and 1.62 +/- 0.10 S.E. respectively. A radiosensitizing effect of pentoxifylline is also evident from the change of the alpha-coefficient which increases from 0.140 to 0.19 and from 0.39 to 0.65 in V79 and Hela cells respectively. In 3 h split dose experiments Hela cells but not V79 cells showed a change in the recovery ratio from 3.0 in control cells to 1.0 in drug exposed cells. In vivo experiments on BALB/c mice receiving 50 mg/kg pentoxifylline alone by subcutaneous injection showed a marked stimulation of tumor growth. When combined with irradiation we observed a 1.3 to 1.7 fold gain in tumor growth delay depending upon tumor size or day of measurement. CONCLUSIONS: The results suggest that pentoxifylline has an intrinsic effect on cell recovery and in tumors also improves blood supply and oxygenation.

Animals↗
PubMed1993

Folding of terminal histone-H1 peptides in the presence of the oligonucleotide 5'-(AT)6-3'.

Peptides H1(1-16) H1(204-218) of human histone H1, comprising the terminal parts of the N- and C-domain, and H1(120-210), comprising the entire C-domain of calf thymus H1, were studied using CD spectroscopy in the presence of trifluoroethanol (TFE) and the oligonucleotide 5'-(AT)6-3'. TFE induces a strong negative ellipticity at 220 nm, showing that the H1 fragments are capable of helical folding. The CD spectrum of free (AT)6 shows strong negative and positive absorptions in the 200-300 nm region resembling the psi-spectrum of DNA. Free (AT)6 showed no helix-coil transition and remained single stranded at room temperature. Combinations of the H1 peptides with increasing concentrations of (AT)6 in low-ionic-strength phosphate buffer developed a strong negative ellipticity at 235 nm. This ellipticity increased with rising (AT)6 concentration and diminished when the (AT)6 concentration exceeded the 1:1 molar ratio in H1(1-16) and H1(204-218) and the 2:1 molar ratio in H1(120-210). The 235 nm ellipticity is attributed to a complex of the H1 peptide with (AT)6 in which the protein is helical. Interaction between histone peptide and (AT)6 is also indicated by UV-absorption spectra which show that the 260 nm absorption is decreased and the 280 nm absorption is increased as compared to free (AT)6. The free peptides show no absorption in this window. The altered 260 and 280 nm absorption suggests that the single-stranded (AT)6 assumes a left-handed pitch and this is confirmed by the displacement of the 270 nm positive ellipticity of free (AT)6 towards 260 nm. Implications of a left-handed linker DNA for chromatin function are discussed.

Amino Acid Sequence↗
PubMed1992

Epitope recognition in histone H1 by SLE autoantibodies in the presence of a DNA-ligand.

To investigate the specificity of anti H1 antibodies peptides from the N- and C-domain of H1 and the synthetic oligonucleotide (AT)6 were complexed. Circular dichroism (CD) spectroscopy indicated that the free peptides H1(1-16), H1(204-218) and C(121-210) in low salt buffer assume a random structure but become helical when bound to the oligonucleotide. The structured and unstructured H1 fragments were then analyzed by enzyme linked immunosorbent assay (ELISA) with anti-H1 antibodies in sera from patients with systemic lupus erythematosis (SLE) and with the monoclonal anti-H1 antibody MRA-12 derived from MLR lpr/lpr autoimmune mice. Binding of these antibodies to H1(204-218) and C was inhibited to a level of 50% when these H1 peptides were complexed with (AT)6. When the same antibody was tested with H1 fragment GC(34-210), attachment to oligonucleotide (AT)6 did not influence antibody binding. Competition studies with liquid phase GC and C antigen against solid phase GC and C indicated that liquid phase GC was more efficient in displacing antibody binding reactivity than liquid phase C. The displacement effect of both liquid phase antigens was greatest against solid phase C. We conclude that anti-H1 autoantibodies are directed against an epitope located near the junction of the G- and C-domain which is exposed and not masked when H1 is bound to DNA.

Autoantibodies↗
PubMed1992

A new face of TB.

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Acquired Immunodeficiency Syndrome↗
PubMed1992

RBE and OER measurements on the p(66) + Be neutron beam at Faure, South Africa.

Results reported are for single dose exposures and refer to 60Co-gamma-irradiation. The RBE determined by V79 cell survival and based on the Do ratio was found to be 1.70 +/- 0.4 ranging from 1.5 to 1.8. In the case of the regeneration of mouse jejunal crypts the RBE was calculated at ten cell survival and was found to be 1.68. The maximum acute mouse skin reaction at a skin score of 2.0 was found to be 2.1 while the average skin reaction was 1.7. Growth retardation of Vicia faba bean roots measured at the level of 50% indicated an average RBE of 3.0 and a range of 2.7 to 3.7. The OER obtained for V79 cell survival was found to be 1.7 to 1.8. Comparison is made with the RBE and OER measurements for the neutron facilities at Clatterbridge, Fermilab and Louvain-la-Neuve which produce neutrons by the same nuclear reaction and whose physical specifications closely resemble those of the Faure neutrons. This comparison indicates that the Faure beam shows no unusual biological features and that its biological effectiveness is in line with that expected from its physical characteristics.

Animals↗
PubMed1990

Hyperprolactinemia in acute myeloid leukemia and indication of ectopic expression of human prolactin in blast cells of a patient of subtype M4.

The sera of 28 patients with acute myeloid leukemia AML--subtypes M1 to M6 were screened for human prolactin (h-PRL). Serum TSH (thyroid stimulating hormone), LH (luteinizing hormone), FSH (follicle stimulating hormone), beta-estradiol, free T4 (tetra-iodotyronine) and testosterone were also determined. It was found that in 16 of the 28 patients h-PRL was significantly elevated while all other endocrine values were normal. In a patient subtype M4 with elevated serum h-PRL we demonstrate by immunoblotting that the hormone and its dimer are present in the blast cells. This may reflect ectopic synthesis due to altered expression of homeobox genes and a requirement of h-PRL as a growth stimulant of the leukemic myeloblast.

Aged↗
PubMed1990

Radiobiological intercomparison of two clinical neutron beams using the regeneration of mouse intestinal crypts.

Determination of dose modification factor greatly facilitates the introduction of clinically proven neutron therapy schedules at new installations. We have compared the biological performance of the p(66)+Be neutron facility at Faure, South Africa, with the established p(65)+Be installation at Louvain-la-Neuve, Belgium. Filtration, D gamma/DT, dose rate and HVT 5/15 for the Louvain and Faure beam are: 2 cm, 2.5 cm polyethylene; 3%, 5%; 0.2 Gy/min, 0.4 Gy/min; and 20 cm and 19 cm respectively. Dosimetry was done in A-150 plastic. Irradiation of BALB/C mice was carried on according to the dose accumulation method in a perspex phantom at 5 cm depth and at an SSD of 150 cm at a field size of 28 X 28 cm2. Sections of the jejunum were prepared at each centre and analyzed by both. The RBE of the Faure beam determined at a survival level of 50 crypts ranged from 1.64 to 1.69. The dose modification factor RBE of the Louvain beam given by Beauduin et al. was 1.61 +/- 0.14. The dose modification factor of the Faure beam relative to the Louvain beam is thus 1.03 +/- 0.13 which could be expected from the similarity of the physical characteristics. Independent RBE measurements in a variety of systems also suggest similar biological properties. The depth variation of the RBE was found to be 4% (mouse gut) using 3 cm polyethylene filter over the depth range of 2.5 to 13.5 cm. This is in agreement with microdosimetry measurements using polyethylene filters of various thicknesses and with V79 measurements reported by Slabbert et al.

Animals↗
PubMed1989

Monoclonal anti-histone H1 autoantibodies from MRL lpr/lpr mice.

Hybridomas producing anti-histone monoclonal antibodies were generated from a 2-month old MRL lpr/lpr mouse. Five IgM antibodies showed binding to histone H3 and three of these IgM antibodies also bound histone H1. Two IgG2a antibodies (MRA3 and MRA12) were specific for histone H1 and their binding was further characterized. Both reacted strongly with mouse and calf thymus histones H1, but showed limited (if any) binding to H1 from non-mammalian species such as duck, trout, or sea urchin sperm. Histone H1 is composed of three domains: N (N-terminal), G (globular) and C (C-terminal). The binding of MRA3 and MRA12 antibodies to the N, G and C domains of the histone H1 molecule was also investigated, using purified H1 fragments. Significant binding was observed only with the GC fragment but not with isolated NG, G or C fragments. Moreover, the integrity of most, if not all, of the G domain (residues 33-122) was necessary for antibody binding, since cleavage of the H1 molecule either at residue 72 or 106 abolished the binding to MRA3 and MRA12. Taken together, these results could indicate that MRA3 and MRA12 antibodies recognize a conformational determinant of the H1 molecule.

Animals↗
PubMed1989

Chromatin decondensed by acetylation shows an elevated radiation response.

V-79 Chinese hamster lung fibroblasts exposed to 5 mM n-sodium butyrate were irradiated with 60Co gamma rays and cell survival was determined by the cell colony assay. In a separate set of experiments the acetylated chromatin obtained from these cells was irradiated and the change of molecular weight of the DNA was evaluated by alkaline sucrose density centrifugation. At a survival level of 10(-2) to 10(-4) cells exposed to butyrate were found to be 1.3-1.4 times more radiosensitive than control cells. Exposure of isolated chromatin to 100 Gy of 60Co gamma irradiation generated 0.9 +/- 0.03 single-strand breaks (ssb) per 10 Gy per 10(8) Da and 2.0 +/- 0.3 ssb/10 Gy/10(8) Da for control and acetylated chromatin, respectively. The elevated radiation sensitivity of chromatin relaxed by acetylation is in good agreement with previous results on chromatin expanded by histone H1 depletion [Heussen et al., Radiat. Res. 110, 84-94 (1987)]. Packing and accessibility of DNA in chromatin appear to be major factors which influence the radiation sensitivity. The intrinsic radiation sensitivity of chromatin in various packing states is discussed in light of the variation of radiation sensitivity of whole cells in the cell cycle which incorporates repair.

Acetylation↗
PubMed1988

Histone H1 structure probed by Staphylococcus aureus V8-proteinase.

Proteolytic digestion of calf thymus histone H1 with Staphylococcus aureus V8-proteinase under structuring conditions generates one major limit peptide P1 which consists of approx. 170 residues. Edman degradation establishes the N-terminal sequence as: Leu-Ile-Thr-Lys-Ala-Val-Ala-Ala-Ser-Lys. Chymotryptic fingerprinting shows that the C-terminal part of the H1 molecule is fully preserved. The peptide therefore comprises the residues H1 (42-210). The Glu-41 cleavage is extremely unusual as it occurs in the structured G-domain which is known to be resistant to proteinases (Hartman, P. G., Chapman, G. E., Moss, T. and Bradbury, E. M. (1977) Eur. J. Biochem. 77, 45-71; Böhm, L., Sautière, P., Cary, P. D. and Crane-Robinson, C. (1982) Biochem. J. 203, 577-582). The V8-proteinase cleavage product H1 (42-210) shows only 20% folding as compared to 95-99% folding shown by the peptides H1 (34-121), H1 (31-210) and H1 (33-210). Folding of the G-domain thus critically depends upon the presence of the eight residues 33-41 amongst which the Gly-Pro-Pro sequence at position 36-38 and a beta-turn predicted at position 35 are considered to be particularly important. The location of the cleavage site in the G-domain renders Staphylococcus aureus V8-proteinase suitable as a structural probe.

Amino Acid Sequence↗
PubMed1987

The relative biological effectiveness of 100 kV X-rays determined by the V-79 cell colony assay.

The relative biological effectiveness (RBE) of 100 kV X-rays compared with cobalt-60-gamma-irradiation was determined using a cell colony assay based on the survival of Chinese hamster V-79 lung fibroblasts. The 37% dose (Do) was found to range from 1.12 to 1.47 and from 1.33 to 1.63 Gy for X-rays and 60Co-gamma-irradiation respectively. The mean RBE value calculated from the Do values was found to be 1.13 +/- 0.04. This figure compares favourably with RBE values calculated from Do values using other endpoints.

Animals↗
PubMed1987

Irradiation damage in chromatin isolated from V-79 Chinese hamster lung fibroblasts.

The effect of chromatin structure on the extent of radiation damage induced by low doses of 100 KeV X rays was investigated using a fluorescent assay for DNA unwinding. Chromatin was isolated from V-79 Chinese hamster lung fibroblast nuclei by partial digestion with micrococcal nuclease. Gel electrophoresis of the isolated DNA showed the molecular weight of the chromatin preparation to be 10.6 X 10(6) with a size range of 6.6-21.7 X 10(6) Da while a size of 10.2 +/- 0.9 X 10(6) Da was found by sedimenting the DNA in alkaline sucrose gradients. The repeat length of V-79 chromatin was found to be 194 +/- 3 bp. The typical nucleosomal repeat structure of the isolated chromatin and that of intact nuclei was identical. Irradiation with 50 and 100 Gy of 100 KeV X rays and analysis by alkaline sucrose density centrifugation indicated that V-79 chromatin sustained 0.56 +/- 0.19 and 0.69 +/- 0.09 single-strand breaks per 10 Gy per 10(8) Da of DNA, respectively. Irradiation with doses of 0.5-3.0 Gy of 100 KeV X rays and analysis by the fluorometric assay showed that the radiation sensitivity of V-79 chromatin decreases sharply on compaction with MgCl2. Histone H1 depletion, which inhibits compaction and causes chromatin to expand by increasing the linker from 26 to 48 bp, results in a considerable increase in the radiation sensitivity. It is concluded that radiation damage sustained by DNA is greatly influenced by chromatin structure.

Animals↗