Linear Dose Dependence Research Articles

A biphasic effect of chlordiazepoxide on animal locomotor activity

Centrally acting drugs often act ‘biphasically’, especially on animal locomotor activities: the same drug stimulates and depresses, depending either on dose or on time since administration. We propose a third, hitherto neglected, type of biphasic effect, well illustrated by chlordiazepoxide, which depends, instead, on the length of time an animal is exposed to a test environment: in an unfamiliar Y-maze, rats' spontaneous locomotion (number of entries into the arms of the Y) was stimulated to begin with, but switched to depression in a few minutes. The stimulant phase appeared to be independent of dose, while the depressant phase showed log linear dose dependence.

The Effects of a Fractionated Gamma Irradiation on Life Shortening and Disease Incidence in BALB/c Mice

BALB/c male mice (12 weeks old) were exposed to a single or fractionated exposure of 137Cs gamma rays. The fractionated dose was split into 10 equal doses delivered at an interval of 1 day. The causes and possible causes of spontaneous death were ascertained by autopsy and histological examination, and the data were treated by competing risk analysis. Life shortening followed a linear dose dependency and was about the same for fractionated (38.1 +/- 3.1 days/Gy) as for single (46.2 +/- 4.3 days/Gy) exposure. Death from tumor disease was enhanced and that from nonstochastic lung and kidney diseases was reduced after fractionated compared to single exposure.

Micronucleus induction in Vicia faba roots. Part 1. Absence of dose-rate, fractionation, and oxygen effect at low doses of low LET radiations.

Micronucleus indication in Vicia faba roots has been evaluated after irradiation with 60Co gamma-rays. The dependence of the damage on dose, dose rate, fractionation, and oxygen has been studied. The best fit to the experimental data in the dose region between 7 and 190 cGy is represented, for single-dose exposures, by a linear + quadratic relationship. In the low-dose region, between 7 and 20 cGy, where the linear dose dependence is dominant, no dose-rate, fractionation, or oxygen effect could be observed. These effects were, however, present in the high-dose region, where the quadratic dependence is dominant.

Dose-dependent induction of metallothionein in kidneys of mice injected with indium and nickel ions.

The induction of renal metallothionein (MT) by indium and nickel loadings was studied by the use of a high performance liquid chromatograph coupled with an atomic absorption spectrophotometer. The amount of MT detected in the kidneys at 24h postinjection showed a linear dose-dependence up to 100 and 260μmol/kg body weight of indium and nickel, respectively, given by intraperitoneal (i.p.) injection. The results suggested that the renall MT was synthesized in the kidneys per se. The quantities of MT induced in the liver and kidneys by indium loading were correlated well with hepatic and renal indium concentrations, respectively, after i.p. or intravenous (i.v.) injection. Although the kidneys accumulated a high concentration of indium after repeated administrations, indium was not detected in the MT fraction on gel filtration chromatography. Only tiny MT peaks were observed at 7 d compared to those at 1 d after a single i.v. injection of indium.

Mechanism of particle track etching in polymeric nuclear track detectors

A mechanism of particle track etching in polymers is proposed, which is based on the assumption that a free reaction volume is required for enhanced chemical degradation in a particle track. The free reaction volume ν ∗ is supposed to be formed from the holes with a free volume ν f, which were produced in the latent track by release of gaseous products of radiolysis or post-irradiation reactions. The exponent in the empirical response function is considered to represent the ratio ν ∗/ν f . The influence of material parameters and etching conditions on the response function of cellulose nitrate track detectors is discussed in terms of the free reaction volume concept. The rapid energy transfer in macromolecules prior to bond cleavage suggests a linear dose dependence of the radiolysis product yield in a wide dose range. The radius restricted energy loss is favoured to be used in response functions from the point of view of radiation chemistry.

Survival and mutagenesis in UV-irradiated phage: multi-hit kinetics of mutation induction and lack of indirect induction by infection with UV-irradiated phage of error-prone repair.

The paper is concerned with the question of whether WEIGLE-reactivation (WR) and WEIGLE-mutagenesis (WM) can be indirectly induced by infection with UV-irradiated phage. Experiments neither with phage lambda of Escherichia coli nor with phage chi of Serratia marcescens show such induction-In this respects phage DNA differs from F'-DNA or Hfr-DNA; possible explanations are discussed. In both systems clear phage mutations can also be induced by UV without irradiation of the host cells; they appear, in unirradiated and irradiated host cells, with an increase of frequency which is greater than proportional to the UV dose. It is concluded that mutation induction of phage in the unirradiated host cells is due to a low level constitutive mutagenic repair; this could either be due to "spontaneous" induction of the mutagenic SOS-function or it could be a mechanism different from this one. Host irradiation would give rise to additional activity by the induced SOS-function leading to WR and WM. It is further concluded that deviation of the induction kinetics from a linear dose-dependence is not due to the necessary induction of SOS-functions.

Ion-beam induced epitaxy of silicon

Epitaxial regrowth of an amorphous Si layer on a 〈100〉 Si crystal held at 200–400°C is achieved under bombardment with Si, Kr, or Xe ions. Channeling measurements with MeV He ions show the regrowth proceeds from the amorphous-crystalline interface, and has an initially linear dose dependence. The annealing beam, however, introduces additional damage centered at or beyond the ion range. Amorphous layers obtained by low-temperature self-ion bombardment regrow much more readily than amorphous deposited layers.

The effects of meal feeding on the incorporation of D-[U- 14C]-glucose into tissue lipids and glycogen as a function of increasing intravenous glucose dose

The in vivo incorporation of D-[U- 14C]-glucose into lipids and glycogen of adipose tissues, muscle tissues, and liver was measured 1 hr after the i.v. injection of increasing glucose doses (0.75, 1.5 and 2.5 g glucose/kg of body weight) in meal-fed and ad libitum-fed rats. In both perirenal and epididymal fat tissue, the levels of 14C-label in the total lipid extract was significantly higher in meal-fed than in nibbling rats at all glucose doses. As the glucose dose increased, the 14C-label in the lipids of both adipose tissues in meal-fed rats increased more than would be expected, assuming a linear dose dependency. In adipose tissues of nibbling rats, glucose dose dependency was linear. The 14C radioactivity in heart muscle lipids was significantly higher in meal-fed rats at all three glucose doses. In the diaphragm, this effect was seen only at the two higher doses; in liver, only at the highest dose; in skeletal muscle, there was no difference at any of the dose levels. The incorporation of 14C-label into tissue glycogen exhibited an entirely different pattern. Muscle glycogen synthesis tended to reach a plateau at the middle glucose dose in meal-fed rats, whereas it increased sharply with increasing glucose dose in nibbling rats. Indeed, muscle glycogen synthesis was much greater in nibbling rats than would be expected, assuming linear dose dependency. It was concluded that the two groups of rats responded quite differently to the increasing glucose load. The excess glucose tended to be incorporated into lipid in meal-fed rats and to muscle glycogen in nibbling rats.

Relation of Ultraviolet Light Mutagenesis to a Radiation-Damage Inducible System in Escherichia coli

Revertants produced by ultraviolet light (uv) were shown to follow a square-law dependence on fluence up to about 0.5 J/m/sup 2/, after which the dependence became closer to linear. This behavior can be associated with an induction process, and a new way of expressing mutation data is presented that allows one to estimate the fraction of cells in a population that is inducible after exposure to a particular uv fluence. Comparison with two other kinds of radiation-induced behavior (induction of inhibition of post-irradiation DNA degradation and induced radioresistance) shows that the fluence dependence of induction is similar in all three cases. A predose with ionizing radiation followed by an incubation period and subsequent exposure to a graded set of uv fluences at 265 nm gave an increase in the number of revertants and a more linear dose dependence. The same result was obtained if the predose was a uv fluence at 265 nm and the graded set of doses was at 313 nm, a wavelength which by itself produces very few revertants. These changes in the mutagenic response were also consistent with the induction of a mutation-potentiating system by the predose. Ultraviolet-produced mutations in the presence or absence of anmore » ionizing radiation predose appear to be due to C ..-->.. T changes in the bacterial genome (C and T denote cytosine and thymine, respectively).« less

The mutagenicity and DNA-damaging activity of cyclic aliphatic sulfuric acid esters

The cyclic aliphatic sulfuric acid esters 1,2-ethylene sulfate (ESF), 1,3-propylene sulfate (PSF) and 1,3-butylene sulfate (BSF) have been tested for their mutagenic and DNA-damaging activity. Mutagenicity of the compounds was established with his-auxotrophic indicator strains of Salmonella typhimurium using the in vitro plate test and the host-mediated assay technique with mice as host animals. The DNA-damaging activity was tested in a repair test with Proteus mirabilis mutants defective in DNA repair. In the repair test with a set of P. mirabilis strains (PG713 hcr −rec − : PG273 hcr +rec + ) PSF and BSF showed a preferential growth inhibition of the repair-defective strain suggesting DNA-damaging activity of these chemicals. No such activity was found for ESF using the same concentrations of 5 and 15 μmol/plate. All cyclic sulfates revert the tester strain TA1535 of S. typhimurium in vitro indicating their ability to induce base substitutions. Compared with the reference compounds dimethyl sulfate (DMS), diethyl sulfate (DES), 1,3-propane sulfone (PPS) and 1,4-butane sulfone (BTS) the mutagenic activity in the plate test can be described as follows: PPS > PSF > BSF > BTS > ESF > DES > DMS. Dose-response studies in the host-mediated assay with tester strain TA1950 of S. typhimurium as genetic indicator system revealed a linear dosedependency of mutagenic activity. For PPS and PSF the lowest effective dose (LED) has been established as 10 μmol/kg. The LED for BSF and BTS was 50 μmol/kg, DMS and DES were mutagenic in doses of 2500 μmol/kg, while ESF was only weakly mutagenic with a LED of 5000 μmol/kg. The dose-response studies in the host-mediated assay and the results obtained in the in vitro spot test demonstrate similarities in the mutagenic action of the cyclic sulfates PSF and BSF and the respective sulfones, while the stronger alkylating compound ESF was a weak mutagen both in vitro and in vivo.

Erratum: Surface depletion region width dependence of threshold voltage shift of ion-implanted MOS transistor

Even under the same implantation conditions, e.g., 50‐keV 11B+ ions implanted through 1100‐A gate oxides on 4‐Ω cm silicon substrates, the threshold voltage shift of n ‐channel MOS transistors is ∼55% of the shift of p ‐channel specimens, and deviation from linear dose dependence is observed for the n channel above a dose of 6×1011/cm2, while for a p ‐channel case the threshold voltage shift depends linearly on the net dose in silicon at least up to 1×1012/cm2. These results are discussed and explained with a calculated dose dependence that accounts for the large decrease of the maximum width of the depletion layer with increasing dose for acceptor‐implanted n ‐channel specimens.

Surface depletion region width dependence of threshold voltage shift of ion-implanted MOS transistor

Even under the same implantation conditions, e.g., 50-keV 11B+ ions implanted through 1100-Å gate oxides on 4-Ω cm silicon substrates, the threshold voltage shift of n -channel MOS transistors is ∼55% of the shift of p -channel specimens, and deviation from linear dose dependence is observed for the n channel above a dose of 6×1011/cm2, while for a p -channel case the threshold voltage shift depends linearly on the net dose in silicon at least up to 1×1012/cm2. These results are discussed and explained with a calculated dose dependence that accounts for the large decrease of the maximum width of the depletion layer with increasing dose for acceptor-implanted n -channel specimens.

The Validity of Risk Estimates of Leukemia Incidence Based on Japanese Data

On the basis of all available pertinent radiobiological evidence it must be expected that the RBE of neutrons for the induction of human leukemia is a function of absorbed dose. An analysis of epidemiological and dosimetric data obtained at Hiroshima and Nagasaki yields results that conform to this expectation. It must, therefore, be concluded that the shapes of the dose-effect curves for the two Japanese cities are different and among the simplest assumptions that may be applied a linear dose dependence for neutrons appears to be the most plausible. Risk estimates based on a linear dependence for gamma radiation must, therefore, be excessive.

Linear and sigmoid dose-effect relations: investigations with gamma-irradiated thymine-(methyl-T) in aqueous solution and in the solid state.

The example of thymine-(methyl-T) demonstrates that in the case of radiation damage to one type of molecule different dose-effect curves will occur depending on the state of the molecule. Radiation-induced tritium cleavage from an aerated aqueous solution of thymine-(methyl-T) shows a linear dose dependence without threshold, tritium cleavage from solid thymine-(methyl-T) follows a sigmoid dose-effect curve with threshold.

Single‐ and double‐strand breaks in 5‐bromouracil‐substituted DNA of B. subtilis and phage PBSH after irradiation with long‐wave length UV and their correlation to intramolecular energy transfer

Abstract5‐Bromouracil‐substituted DNA was isolated form B. Subtilis and phage PBSH. The three DNA fractions of Different densities (TT, TB, and BB) were irradiated with u.v. (313nm). The number of single‐strand and double‐strand breaks was determined. The breakage rates are given. It was found that in hybrid DNA (TB) double‐strand breaks occur depending linearly on dose. In BB–DNA the observed double‐Strand bresks can be divided into two fractions with a linear and quadratic dose dependence respectively. The results can be explained by assuming intramolecular energy transfer from the BU‐containing strand to its complementary strand.

Excitonic Processes and Thermoluminescence

Processes of defect creation by nonionizing radiation were studied by applying thermoluminescence methods. KBr crystals were irradiated at 80 K by monochromatic uv light in the region of 1800-2300 \AA{}. Shapes of glow curves were found to differ from those obtained after $x$ coloration. Excitation spectra of the various glow peaks as well as dose dependence of their intensities were investigated. The excitation spectrum showed maxima at the $\ensuremath{\alpha}$ band and on the long-wavelength tail of the fundamental absorption. Most of the glow peaks showed a linear dose dependence. The mechanism proposed by Pooley and by Hersh is extended to the case of defect creation by irradiation into a perturbed exciton state and excitation of thermoluminescence. An expression for the number of the defects created by the uv irradiation is derived as a function of the radiation dose. This expression takes into account the absorption coefficient of the crystal and, therefore, the penetration depth of the exciting monochromatic light. Experimental results were found to be in good agreement with those predicted by the model.

Superlinear dose dependence of thermoluminescence in KBr

The dependence of thermoluminescence intensities on the dose of the exciting radiation was studied in u.v. irradiated KBr crystals. Most of the glow peaks revealed a linear dose dependence. The intensity of the 150°K glow peak was found to depend quadratically on the dose. A two stage process is suggested for the excitation of this glow peak.

Zur Dosis-Effekt-Beziehung*

Erstmalig wurde an einem somatischen Strahlenschaden, der Gewichtsveränderung der Augenlinse, ein wechselhaftes Verhalten der Dosis-Effekt-Beziehung nachgewiesen. Eine lineare Dosisabhängigkeit konnte als Zwischenphase innerhalb eines gesetzmäßigen Reaktionsablaufes statistisch weitgehend als reell gesichert werden. Abschließend werden verschiedene sich hieraus ergebende Probleme erörtert.