The r.b.e. of different energy neutrons as measured by the heamatopoietic spleen-colony technique.

The spleen-colony technique has been used for determining the relative biological effectiveness (r.b.e.) for several energies of neutron radiation. Donor mice were exposed for fission and accelerator-generated neutrons at a variety of doses and energies. Immediately after exposure, donor bone-marrow was removed from the hind legs, and standard amounts were injected intravenously into lethally X-irradiated recipients. After 7 days the recipients spleens were evaluated for surface colonies. Dose-response curves were obtained for each type of radiation and the Do was determined. The neutron r.b.e. values from the Do compared with 250kVp X-rays were: reactor 1.58, 252Cf 1:59, and accelerator varied from 2.85 at 1.0 Mev to 0.85 at 13.4 MeV.     

Calculation of clinical r.b.e. values for neutrons

A method is described for calculating r.b.e. values for normal tissues at risk in clinical neutron beam therapy. This is based on the assumption that with high l.e.t. radiations the slope of the cell survival curve is steeper, mainly in the initial or low-dose region. This effect is quantified by using two coefficients, one (epsilon) to produce a proportionate increase in the initial slope, and a second (eta) determining the change in the terminal slope (D0) of the survival curve. Analysis of published experimental data shows epsilon to be a variable quantity, different for different tissues; epsilon is larger when the survival curve has a large shoulder or slope ratio (rho). By contrast, eta is relatively constant (for a given beam) and less dependent on the tissue or end-point studied. For low doses, the r.b.e. approaches epsilon, which can be calculated given eta (characteristic of the beam) and rho (characteristic of the relevant tissue) [epsilon = eta + rho(eta - 1)]. This provides a useful approximation to the clinical r.b.e. for specific tissues relative to conventionally fractionated low-l.e.t. photons.     

Somatic aberration induction in Tradescantia occidentalis by neutrons, x- and gamma-radiations. II. Biological results, r.b.e. and o.e.r.

Biological results, including statistical features, are described for the irradiation of Tradescantia occidentalis with 250 kVp X-rays, cobalt-60 gamma-radiation and monoenergetic neutrons with energies between 0-08 and 15 MeV. The effect studied was that of the induction of pink sectors in the otherwise blue staminal hairs of the flowers at low doses of radiation. Statistical aspects of the results suggest that a fraction of the asynchronous cell population in the hairs is very sensitive to neutron radiation, but not necessarily to lower LET radiations. All the results were fitted by a least-squares method by polynomials of different degrees. Best fits to X- and gamma-ray data were provided by second-degree polynomials, and to the neutron data by either second- or third-degree polynomials. Limiting r.b.e. and o.e.r. values at low doses are derived. Some computed microdosimetric parameters are presented in comparison with the r.b.e. values. It is concluded that the effect studied is complex and may not provide a critical test of bio-physical theories of radiation effects.     

Photochemistry of pyrimidine bases as studied by e.s.r. and spin-trapping

The direct photoexcitation of pyrimidine bases in D2O solutions yields free radicals which could be conveniently identified by spin-trapping with 2-methyl-2-nitrosopropane. Most of the radicals formed were attributed to D-addition to one end of the 5,6 double bond. However, orotic acid and iso-orotic acid yielded N(3) centred free radicals, formed by homolytic cleavage of the N-H bond. No indication could be found for a free radical involvement in the photocleavage of cyclobutane-type pyrimidine dimers.     

The r.b.e. of fast fission neutrons (2 MeV) for chronic radiation damage of the large bowel of rats after single dose and fractionated irradiation

Late damage in the rectum of rats was studied after local irradiation with 2 MeV fast fission neutrons and the results were compared with those for 300 kV X-rays. A similarity between latency times, and between clinical, gross pathological and histological appearances of the rectal obstruction after the two types of radiation was observed. The r.b.e. evaluated from ED 50/200 days values was 1.8 for single doses, 2.1 for two fractions and 3 for five fractions and these are similar to r.b.e.s from other investigations of chronic intestinal radiation damage. Using linear quadratic analysis, a limiting r.b.e. of 5 was obtained. The beta-values are similar for both radiation qualities. Because of the high gamma-contamination (25 per cent) in the RENT I beam a possible correction of the r.b.e. for neutrons only, assuming interaction, is discussed.     

The conformation of bombesin in solution as determined by two-dimensional 1H-NMR techniques

The 1H nuclear magnetic resonance spectrum of the tetradecapeptide, bombesin, has been assigned in (2H6)dimethyl sulphoxide solution and aqueous solution using two-dimensional techniques. The chemical shifts in both solvents indicate that the molecule has little secondary structure and adopts a random coil conformation. A comparison is made between the spectra of various smaller bombesin fragments and the intact polypeptide.     

R.b.e. and o.e.r. of extended-Bragg-peak helium ions: survival and development of rat embryos.

Rats were exposed under aerobic or hypoxic conditions to 200-1200 rads of 60Co gamma-rays or extended-Bragg-peak helium ions on the eighth day of gestation. Uterine contents were examined on the twentieth day of gestation. At the 50 per cent embryonic survival level, helium ion r.b.e. was 1(.0) (aerobic) and 1(.2) (hypoxic). Maximum attainable gamma-ray and helium-ion o.e.r.s. were 2(.2) and 1(.7) respectively, indicating an oxygen-effect gain (o.e.g.) of 1(.2). At the 10 per cent survival level helium ion r.b.e. was 1(.1) (aerobic) and 1(.4) (hypoxic). Gamma-ray and helium-ion 0.e.r.s. were 2(.0) and 1(.5) respectively, indicating a helium ion o.e.g. of 1(.3). These data demonstrate that the small fraction of high-LET radiation present in this helium ion beam has a neglible effect on the aerobic r.b.e., but lowers the effective o.e.r. of the beam approximately 25 per cent relative to that of gamma-rays. Helium ions were significantly more effective than gamma-rays in killing embryos under hypoxic conditions, in producing congenital abnormalities under aerobic conditions, and in stunting foetal growth under both conditions.     

The purity of tritiated tetrodotoxin as determined by bioassay.

The radioactivity binding of a tritiated tetrodotoxin preparation to an electric organ particulate fraction was compared with the binding of biological activity as determined by biological assay. This comparison shows that the chromatographically homogeneous toxin contained a large proportion of radioactive impurities which bind nonspecifically to the electroplax preparation.     

The relative biological effectiveness of low doses of 14 MeV neutrons in steady-state murine spermatogenesis as determined by flow cytometry

The relative biological effectiveness of 14 MeV neutrons in the low-dose range < or =1 Gy has been determined in differentiating and differentiated spermatogonia. Male NMRI mice were exposed to single doses of 2 cGy to 3 Gy of (60)Co gamma rays or neutrons. The ratios of testicular S-phase cells, 4c primary spermatocytes, and elongated spermatids were quantified by DNA flow cytometry 2 to 70 days after irradiation and were found to decrease. Histological samples and testis weight were analyzed in parallel. Doses of 2-5 cGy neutrons and 10-50 cGy gamma rays significantly (P<0.05) decreased the proportions of S-phase cells, spermatocytes and elongated spermatids at 4, 14 and 28 days postirradiation. For S-phase cells, the biphasic shape of the cell survival curves was described with a D(50) of 5 cGy neutrons. The D(50) for (60)Co gamma rays and the relative biological effectiveness could not be determined. The relative biological effectiveness of neutrons at 50% reductions of testis weight, primary spermatocytes, and elongated spermatids were 2.5, 10.0 and 6.1, respectively. This in vivo assay is interesting because of its sensitivity at dose ranges that are relevant for exposures in the environment, the workplace and radiotherapy.     

The structure of human tripeptidyl peptidase II as determined by a hybrid approach

Tripeptidyl-peptidase II (TPPII) is a high molecular mass (～5 MDa) serine protease, which is thought to act downstream of the 26S proteasome, cleaving peptides released by the latter. Here, the structure of human TPPII (HsTPPII) has been determined to subnanometer resolution by cryoelectron microscopy and single-particle analysis. The complex is built from two strands forming a quasihelical structure harboring a complex system of inner cavities. HsTPPII particles exhibit some polymorphism resulting in complexes consisting of nine or of eight dimers per strand. To obtain deeper insights into the architecture and function of HsTPPII, we have created a pseudoatomic structure of the HsTPPII spindle using a comparative model of HsTPPII dimers and molecular dynamics flexible fitting. Analyses of the resulting hybrid structure of the HsTPPII holocomplex provide new insights into the mechanism of maturation and activation.     

Structural determination of alginic acid and the effects of calcium binding as determined by high-field n.m.r.

The nature of the solution conformations of the alginic acid components D-mannuronan (poly-ManA) and L-guluronan (poly-GulA) from Azotobacter vinelandii were investigated by both one- and two-dimensional n.m.r. methods. Unequivocal proton assignments for both polymers as well as their constituent monomer units were made based on chemical-shift theory, coupling constant analysis, and nuclear Overhauser enhancement measurements. These data were used to investigate the interactions of poly-GulA and poly-ManA with Ca2+ ion in aqueous medium. Based on relative crosspeak integrals measured in two-dimensional phase-sensitive NOESY spectra of free and calcium-bound polymer, a model for calcium binding is proposed.