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Instrument dependence of electrospray ionization and tandem mass spectrometric fragmentation of the gingerols.

The gingerols, including [6]-, [8]-, and [10]-gingerols, a series of chemical homologs differentiated by the length of their unbranched alkyl chains, have been identified as major active components in fresh ginger rhizome. The purpose of this study was to investigate the utility of ion trap liquid chromatography/tandem mass spectrometry (LC/MS/MS) as an online tool to identify and quantify these compounds in raw or processed ginger rhizome samples. Negative mode electrospray ionization (ESI) was used in MS, MS/MS and MS(n) experiments in quadrupole ion trap instruments from two different manufacturers and in high-resolution and accurate mass MS and MS/MS experiments in a Fourier transform ion cyclotron resonance mass spectrometer to elucidate the ionization and fragmentation mechanisms of these compounds in these instruments. Positive mode ESI, which generated many more fragment ions in full scan MS even under gentle ionization conditions, was also used in LC/MS and MS/MS experiments and in direct infusion MS and MS/MS experiments. Consistent and predictable ionization and fragmentation behaviors were observed for all gingerols when analyzed in the same instrument. Instruments from different manufacturers, however, had different ionization mechanisms. The major difference between instruments was their ability to form covalent dimer adducts of the gingerols. Subsequent fragmentation patterns of the precursor ions were essentially identical. These results clearly demonstrate that LC/MS instruments produce data that cannot necessarily be replicated in other laboratories, especially if those laboratories do not have the same instrument model from the same manufacturer. This presents major problems for metabolite target analysis, metabolic profiling and metabolomics investigations, which would benefit from LC/MS mass spectrum libraries as they do from GC/MS mass spectrum libraries, because such libraries may not be valid across platforms.

Catechols↗

The shielding effect of glycerol against protein ionization in electrospray mass spectrometry.

Most commercial recombinant proteins used as molecular biology tools, as well as many academically made preparations, are generally maintained in the presence of high glycerol concentrations after purification to maintain their biological activity. The present study shows that larger proteins containing high concentrations of glycerol are not amenable to analysis using conventional electrospray ionization mass spectrometry (ESI-MS) interfaces. In this investigation the presence of 25% (v/v) glycerol suppressed the signals of Taq DNA polymerase molecules, while 1% (v/v) glycerol suppressed the signal of horse heart myoglobin. The signal suppression was probably caused by the interaction of glycerol molecules with the proteins to create a shielding effect that prevents the ionization of the basic and/or acidic groups in the amino acid side chains. To overcome this difficulty the glycerol concentration was decreased to 5% (v/v) by dialyzing the Taq polymerase solution against water, and the cone voltage in the ESI triple-quadrupole mass spectrometer was set at 80-130 V. This permitted observation of a mass spectrum that contained ions corresponding to protonation of up to 50% of the ionizable basic groups. In the absence of glycerol up to 85% of the basic groups of Taq polymerase became ionized, as observed in the mass spectrum at relatively low cone voltages. An explanation of these and other observations is proposed, based on strong interactions between the protein molecules and glycerol. For purposes of comparison similar experiments were performed on myoglobin, a small protein with 21 basic groups, whose ionization was apparently suppressed in the presence of 1% (v/v) glycerol, since no mass spectrum could be obtained even at high cone voltages.

Animals↗

Formation of ionization clusters in nanometric structures of propane-based tissue-equivalent gas or liquid water by electrons and alpha-particles.

Despite the importance of ionization yield formation in sub-cellular structures a few nanometres in size, with regard to radiation damage our present knowledge in this respect is almost exclusively based on Monte Carlo simulations which in turn are based on cross section sets for water vapour or liquid water. Experimental data, although urgently needed, are still missing because the direct measurement of ionization yields in sub-cellular structures or, at least, in nanometric volumes of liquid water, is not yet possible. The best feasible way to overcome this problem of measurement at present, is the use of highly sophisticated counters filled with gases at low operating pressure to simulate target volumes a few nanometres in diameter at unit density. An indispensable prerequisite of the reliability of such measurements is, however, a check of the equivalence of the ionization yield produced in a specified target gas and the yield to be expected in liquid water or biological material. For this purpose, the ionization yield formation by electrons and alpha-particles in liquid water was simulated using the Monte Carlo method and compared with that produced in propane-based tissue-equivalent gas (composition by volume 55% C3H8, 39.6% CO2, 5.4% N2). After a short summary of the most important physical aspects of ionization cluster formation, new results are presented and discussed from the point of view of radiation physics and radiation biology.

Alpha Particles↗

Sensitivity enhancement in liquid chromatography/atmospheric pressure ionization mass spectrometry using derivatization and mobile phase additives.

High performance liquid chromatography with atmospheric pressure ionization (API) mass spectrometry has been essential to a large number of quantitative analytical applications for a variety of compounds. Poor detection sensitivity however is a problem observed for a number of analytes because detection sensitivity can be affected by many factors. The two most critical factors are the chemical and physical properties of the analyte and the composition of the mobile phase. In order to address these critical factors which may lead to poor sensitivity, either the structure of the analyte must be modified or the mobile phase composition optimized. The introduction of permanently charged moieties or readily ionized species may dramatically improve the ionization efficiency for electrospray ionization (ESI), and thus the sensitivity of detection. Detection sensitivity may also be enhanced via introduction of moieties with high proton affinity or electron affinity. Mobile phase component modification is an alternative way to enhance sensitivity by changing the form of the analytes in solution thereby improving ionization efficiency. pH adjustment and adduct formation have been commonly used to optimize detection conditions. The sensitivity of detection for analytes in bio-matrices could also be enhanced by decreasing ion-suppression from the matrix through derivatization or mobile phase addition. In this review, we will discuss detection-oriented derivatization as well as the application of mobile phase additives to enhance the sensitivity of detection in liquid chromatograph/atmospheric ionization/mass spectrometry (LC/API/MS), focusing in particular on the applications involving small molecules in bio-matrices.

Alcohols↗

Adduct formation in electrospray ionization mass spectrometry II. Benzoic acid derivatives.

This work serves as a follow-up to Part I of experiments designed to determine the underlying principles in the formation of pseudomolecular, or adduct, ions during electrospray ionization. Aromatic acids were studied by flow injection analysis in the negative ionization mode of electrospray ionization mass spectrometry. Part I dealt with common acidic anti-inflammatory pharmaceuticals. such as ibuprofen and related analogues. Part II deals with functionally less complex molecules, namely benzoic acid (BA) and substituted benzoic acids. Halide-substituted molecules are investigated to deduce the effect of electron-withdrawing substituents (bromo-, chloro-, and fluoro-) and ring position (ortho-, meta- and para-) on the response of a traditional deprotonated molecular ion ([M-H]-) and a sodium-bridged dimer ion ([2M-2 H+Na]-). Amino-substituted benzoic acids are also analyzed in order to study the effect of an additional ionizable group on the molecule, and para-tert.-butyl-BA is analyzed to study the effect of increased hydrophobicity, as they relate to the formation of pseudomolecular ions. This study shows that solution character [octanol-water partition coefficient (or log P) and pKa] of the model compounds controls the relative efficiency of formation of [M-H]- and [2M-2H+Na]- ions. However the relative gas phase character (gas phase basicity and proton affinity) also has a significant effect on the formation of the sodium-bridged dimer ion. For the halide-substituted species, placement of the electron-withdrawing atom at the meta-position gives the greatest enhancement in sensitivity. Observations also show that as the structural complexity of the model compound increases, predictions relating analyte acidity to sodium-bridged dimer ion formation give way to a stronger dependence between log P values and ionization efficiency. Supporting this hypothesis is the nearly ten-fold enhancement in signal for tert.-butyl BA relative to BA. due to the greater hydrophobicity, and consequently, increased surface activity in an electrosprayed droplet of the analyte molecule.

Benzoic Acid↗

Stability studies of propoxur herbicide in environmental water samples by liquid chromatography-atmospheric pressure chemical ionization ion-trap mass spectrometry.

Liquid chromatography-atmospheric pressure ionization ion-trap mass spectrometry has been investigated for the analysis of polar pesticides in water. The degradation behavior of propoxur, selected as a model pesticide belonging to the N-methylcarbamate group, in various aqueous matrices (Milli-Q water, drinking water, rain water, seawater and river water) was investigated. Two interfaces of atmospheric pressure ionization, atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI), were compared during the study. Propoxur and its transformation product (N-methylformamide) were best ionized as positive ions with both APCI and ESI, while another transformation product (2-isopropoxyphenol) yielded stronger signals as negative ions only with APCI. In addition, the effects of various pH, matrix type and irradiation sources (sunlight, darkness, indoor lighting and artificial UV lamp) on the chemical degradation (hydrolysis) were also assessed. From the kinetic studies of degradation, it was found that the half-life of propoxur was reduced from 327 to 161 h in Milli-Q water with variation of irradiation conditions from dark to sunlight exposure. Degradation rates largely increased with increasing pH. The half-life of the target compound dissolved in Milli-Q water under darkness decreased from 407 to 3 h when the pH of Milli-Q water was increased from 5 to 8.5. These suggest that hydrolysis of propoxur is light-intensity and pH-dependent. In order to mimic contaminated natural environmental waters, propoxur was spiked into real water samples at 30 microg/l. The degradation of propoxur in such water samples under various conditions were studied in detail and compared. With the ion trap run in a time-scheduled single ion monitoring mode, typical limits of detection of the instrument were in the range of 1-10 microg/l.

Atmospheric Pressure↗

Effect of the location of hydrogen abstraction on the fragmentation of diuretics in negative electrospray ionization mass spectrometry.

The diuretic agents bumetanide, xipamide, indapamide, and related compounds were investigated in order to determine the effect of different ionization sites on their collisionally activated dissociation and the corresponding fragmentation pathways. Therefore, analytes were selectively alkylated, and structural analogues as well as deuterium labeled compounds synthesized, which contain a reduced number of ionizable hydrogen atoms. Thus, specific hydrogen abstractions and their correlated dissociation routes of the negatively charged molecules were eliminated, providing evidence for the influence of the location of ionization on product ion spectra. Fragment ions such as m/z 78 indicate ionization at the commonly present sulfamoyl residue of diuretics but does not exclude additional ionization sites. Product ion spectra of the investigated diuretic agents proved to be composed by fragmentations initiated from different hydrogen abstractions. Moreover, the generation of radical anions by collision-activated dissociation of even-electron precursor ions was observed, the generation of which is discussed by proposed fragmentation pathways.

Bumetanide↗

Matrix effect in bio-analysis of illicit drugs with LC-MS/MS: influence of ionization type, sample preparation, and biofluid.

The purpose of the present work was to evaluate the synergistic effect of ionization type, sample preparation technique, and bio-fluid on the presence of matrix effect in quantitative liquid chromatography (LC)-MS/MS analysis of illicit drugs by post-column infusion experiments with morphine (10-microg/mL solution). Three bio-fluids (urine, oral fluid, and plasma) were pretreated with four sample preparation procedures [direct injection, dilution, protein precipitation, solid-phase extraction (SPE)] and analyzed by both LC-electrospray ionization (ESI)-MS/MS and LC-atmospheric pressure chemical ionization (APCI)-MS/MS. Our results indicated that both ionization types showed matrix effect, but ESI was more susceptible than APCI. Sample preparation could reduce (clean up) or magnify (pre-concentrate) matrix effect. Residual matrix components were specific to each bio-fluid and interfered at different time points in the chromatogram. We evaluated matrix effect in an early stage of method development and combined optimal ionization type and sample preparation technique for each bio-fluid. Simple dilution of urine was sufficient to allow for the analysis of the analytes of interest by LC-APCI-MS/MS. Acetonitrile protein precipitation provided both sample clean up and concentration for oral fluid analysis, while SPE was necessary for extensive clean up of plasma prior to LC-APCI-MS/MS.

Analgesics, Opioid↗

Factors affecting quantitative analysis in laser desorption/laser ionization mass spectrometry.

Microprobe laser desorption/laser ionization mass spectrometry (microL(2)MS) is a sensitive and selective technique that has proven useful in the qualitative and semiquantitative detection of trace organic compounds, particularly polycyclic aromatic hydrocarbons (PAHs). Recent efforts have focused on developing microL(2)MS as a quantitative method, often by measuring the ratio of signal strength of an analyte to an internal standard. Here, we present evidence of factors that affect these ratios and thus create uncertainty and irreproducibility in quantification. The power and wavelength of the desorption laser, the delay time between the desorption and ionization steps, the power of the ionization laser, and the ionization laser alignment are all shown to change PAH ratios, in some cases by up to a factor of 24. Although changes in the desorption laser parameters and the delay time cause the largest effects, the ionization laser power and alignment are the most difficult parameters to control and thus provide the most practical limitations for quantitative microL(2)MS. Variation in ratios is seen in both synthetic poly(vinyl chloride) membranes and in "real-life" samples of Murchison meteorite powder. Ratios between similar PAHs vary less than those between PAHs that differ greatly in mass and structure. This finding indicates that multiple internal standards may be needed for quantification of samples containing diverse PAHs.

Polycyclic Aromatic Hydrocarbons↗

Electrosonic spray ionization. A gentle technique for generating folded proteins and protein complexes in the gas phase and for studying ion-molecule reactions at atmospheric pressure.

Electrosonic spray ionization (ESSI), a variant on electrospray ionization (ESI), employs a traditional micro ESI source with supersonic nebulizing gas. The high linear velocity of the nebulizing gas provides efficient pneumatic spraying of the charged liquid sample. The variable electrostatic potential can be tuned to allow efficient and gentle ionization. This ionization method is successfully applied to aqueous solutions of various proteins at neutral pH, and its performance is compared to that of the nanospray and micro ESI techniques. Evidence for efficient desolvation during ESSI is provided by the fact that the peak widths for various multiply charged protein ions are an order of magnitude narrower than those for nanospray. Narrow charge-state distributions compared to other ESI techniques are observed also; for most of the proteins studied, more than 90% of the protein ions can be accumulated in one charge state using ESSI when optimizing conditions. The fact that the abundant charge state is normally as low or lower than that recorded by ESI or nanospray indicates that folded protein ions are generated. The sensitivity of the ionization technique to high salt concentrations is comparable to that of nanospray, but ESSI is considerably less sensitive to high concentrations of organic additives such as glycerol or 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris base). Noncovalent complexes are observed in the case of myoglobin, protein kinase A/ATP complex, and other proteins. The extent of dissociation of protein ions in ESSI is comparable to or even smaller than that in the case of nanospray, emphasizing the gentle nature of the method. The unique features of ESSI are ascribed to very efficient spraying and the low internal energy supplied to the ions. Evidence is provided that the method is capable of generating fully desolvated protein ions at atmospheric pressure. This allows the technique to be used for the study of ion-molecule reactions at atmospheric pressure and examples of this are shown.

Atmospheric Pressure↗

Increase of NKG2D ligands and sensitivity to NK cell-mediated cytotoxicity of tumor cells by heat shock and ionizing radiation.

In this study, we have investigated if current cancer therapeutic modalities including hyperthermia and ionizing radiation can increase the expression of NKG2D ligands in human cancer cell lines. The expressions of NKG2D ligands were induced by both heat shock and ionizing radiation in various cell lines including KM12, NCI-H23, HeLa and A375 cells with peaks at 2 h and 9 h after treatment, respectively, although inducibility of each NKG2D ligand was various depending on cell lines. During the induction of NKG2D ligands, heat shock protein 70 was induced by heat shock but not by ionizing radiation. These results were followed by increased susceptibilities to NK cell-mediated cytolysis after treatment with heat shock and ionizing radiation. These results suggest that heat shock and ionizing radiation induce NKG2D ligands and consequently might lead to increased NK cell-mediated cytotoxicity in various cancer cells.

Antigens, Surface↗

Direct determination of the ionization energies of FeO and CuO with VUV radiation.

Photoionization efficiency curves were measured for gas-phase FeO and CuO using tunable vacuum-ultraviolet radiation at the Advanced Light Source. The molecules are prepared using laser ablation of a metal-oxide powder in a novel high-repetition-rate source and are thermally moderated in a supersonic expansion. These measurements provide the first directly measured ionization energy for CuO, IE(CuO)=9.41 +/- 0.01 eV. The direct measurement also gives a greatly improved ionization energy for FeO, IE(FeO) = 8.56 +/- 0.01 eV. The ionization energy connects the dissociation energies of the neutral and cation, leading to a refined bond strength for the FeO cation: D0(Fe(+)-O)=3.52 +/- 0.02 eV. A dramatic increase in the photoionization cross section at energies of 0.36 eV above the threshold ionization energy is assigned to autoionization and direct ionization involving one or more low-lying quartet states of FeO+. The interaction between the sextet ground state and low-lying quartet states of FeO+ is key to understanding the oxidation of hydrogen and methane by FeO+, and these experiments provide the first experimental observation of the low-lying quartet states of FeO+.

Computer Simulation↗

Effects of ionization on N-glycylglycine peptide: influence of intramolecular hydrogen bonds.

The ionization effects on 28 conformations of N-glycylglycine are analyzed by means of the hybrid B3LYP and the hybrid meta-MPWB1K density functionals and by single-point calculations at the CCSD(T) level of theory. The most favorable process observed corresponds to the ionization of the only neutral conformation that presents a OH...NH2 intramolecular hydrogen bond, which leads to CO2 elimination after a spontaneous proton transfer from -COOH to NH2. The remaining neutral structures evolve to 20 different conformations of N-glycylglycine radical cation, which lie about 25-40 kcal/mol higher than the decarboxylated [NH3CH2CONHCH2]+*...[CO2] complex. Structural changes induced by ionization depend on the intramolecular hydrogen bonds of the initial conformation, since they determine the nature of the electron hole formed. In most cases, ionization takes place at the terminal -NH2 and -CO of the amide bond, which produces a strengthening of the peptide bond and the formation of new -NH2...OC(amide) and -NH2...OCOH hydrogen bonds. However, if -NH2 and -CO(amide) simultaneously act as proton acceptor in the neutral conformation, ionization is mainly localized at the carboxylic group, which produces a strengthening of the -COOH...OC(amide) bond. Both functionals lead to similar trends and compare well with CCSD(T) results except for a few cases for which B3LYP provides a too delocalized picture of the electron hole and consequently leads to artificial geometry reorganization.

Air Ionization↗

Low dose ionizing radiation-induced activation of connexin 43 expression.

PURPOSE: Connexin 43 has been implicated in the cellular response to ionizing radiation by enabling cell-to-cell communication. It is established here that the expression of connexin 43 is affected by ionizing radiation and the mechanism involved is investigated. MATERIALS AND METHODS: The human connexin 43 promoter was cloned into a Luciferase reporter plasmid and activation by ionizing radiation was measured in normal human fibroblasts as well as HeLa cells. The regions responsible for the radiation inducibility were defined using deletion and point mutations of the construct. The results were confirmed by Northern and Western blotting. RESULTS: Ionizing radiation activates the human connexin 43 promoter in a time- and dose-dependent manner with a maximal induction (4.2-fold +/-0.58) after 6 h and a dose of 0.5 Gy. Higher doses up to 5 Gy led to a less marked increase (2-fold) over the same period. This promoter activation was associated with comparable increases in both connexin 43 mRNA and protein levels. The low dose radiation response of the promoter is mainly dependent on consensus binding sites for nuclear factor of activated T-cells (NFAT) and activator protein (AP1) in a region -2537 and -2110 bp from the transcriptional start site as determined by mutation analysis. CONCLUSIONS: Low doses of ionizing radiation induce the transcriptional upregulation of connexin 43 expression employing NFAT and AP1 sites.

Amino Acid Sequence↗

Dosimetry using plane-parallel ionization chambers in a 75 MeV clinical proton beam.

Reference ionization chamber dosimetry in clinical proton beams is generally performed with cylindrical ionization chambers. However, when the measurement is performed in the presence of a large depth dose gradient or in a narrow spread out Bragg peak (SOBP), it could be advisable to use a plane-parallel chamber. Few recommendations and studies have been devoted to this subject. In this paper, experimental information on perturbation correction factors for four plane-parallel ionization chamber types in proton beams is presented. The experiments were performed in 75 MeV modulated and non-modulated proton beams. Monte Carlo calculations have been performed to support the conclusions of the experimental work. Overall, we were not able to find experimental evidence for significant differences between the secondary electron perturbation correction factors for plane-parallel chambers and those for a cylindrical NE2571. We found experimental ratios of perturbation correction factors that did not differ by more than 0.6% from unity for a Roos and two NACP02 chambers, and by not more than 1.2% for a Calcam-2 and two Markus chambers. Monte Carlo simulations result in corrections that are limited to 0.6% in absolute value, but given the overall uncertainties of the measurements, the deviations of the correction factors from unity could not be resolved from the experimental results. The results of the simulations thus support the experimental conclusion that perturbation correction factors for the set of plane-parallel chambers in both proton beams (relative to NE2571) do not deviate from unity by more than 1.2%. This confirms, within the experimental uncertainties, the assumption that the overall perturbation correction factor for a plane-parallel chamber in a low-energy proton beam is unity, made in IAEA TRS-398 and other dosimetry protocols. Given the large uncertainties of the gradient correction factors to be applied when using a cylindrical ionization chamber in a narrow SOBP or in the presence of a strong depth dose gradient, the level of agreement between plane-parallel and cylindrical ionization chambers observed in this study shows that plane-parallel chambers are a reliable alternative for reference dosimetry in low-energy proton beams.

Calibration↗

Down syndrome and ionizing radiation.

This review examines the epidemiologic and experimental studies into the possible role ionizing radiation might play in Down Syndrome (trisomy 21). It is prompted by a report of a temporal cluster of cases of this chromosomal disorder observed in West Berlin exactly 9 mo after the radioactive cloud from Chernobyl passed. In approximately 90% of cases, Down Syndrome is due to the nondisjunction of chromosome 21, most often in the oocyte, which may be exposed to ionizing radiation during two separate periods: before the completion of the first meiosis or around the time of ovulation. Most epidemiologic studies into trisomies and exposure to ionizing radiation examine only the first period; the Chernobyl cluster is related to the second. Analysis of these epidemiologic results indicates that the possibility that ionizing radiation might be a risk factor in Down Syndrome cannot be excluded. The experimental results, although sometimes contradictory, demonstrate that irradiation may induce nondisjunction in oogenesis and spermatogenesis; they cannot, however, be easily extrapolated to humans. The weaknesses of epidemiologic studies into the risk factors for Down Syndrome at birth (especially the failure to take into account the trisomy cases leading to spontaneous abortion) are discussed. We envisage the utility and feasibility of new studies, in particular among women exposed to prolonged or repeated artificially-produced ionizing radiation.

Animals↗

Ionizing radiation alters the properties of sodium channels in rat brain synaptosomes.

The effect of ionizing radiation on neuronal membrane function was assessed by measurement of neurotoxin-stimulated 22Na+ uptake by rat brain synaptosomes. High-energy electrons and gamma photons were equally effective in reducing the maximal uptake of 22Na+ with no significant change in the affinity of veratridine for its binding site in the channel. Ionizing radiation reduced the veratridine-stimulated uptake at the earliest times measured (3 and 5 s), when the rate of uptake was greatest. Batrachotoxin-stimulated 22Na+ uptake was less sensitive to inhibition by radiation. The binding of [3H]saxitoxin to its receptor in the sodium channel was unaffected by exposure to ionizing radiation. The effect of ionizing radiation on the lipid order of rat brain synaptic plasma membranes was measured by the fluorescence polarization of the molecular probes 1,6-diphenyl-1,3,5-hexatriene and 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene. A dose of radiation that reduced the veratridine-stimulated uptake of 22Na+ had no effect on the fluorescence polarization of either probe. These results demonstrate an inhibitory effect of ionizing radiation on the voltage-sensitive sodium channels in rat brain synaptosomes. This effect of radiation is not dependent on changes in the order of membrane lipids.

Animals↗

Nurture with ionizing radiation: a provocative hypothesis.

Whole body exposure to low-dose ionizing radiation appears to decrease overall cancer incidence. The data come from at least eight large studies of populations exposed to various forms of radioactive material and from more limited studies of occupational and environmental exposures to plutonium, radium, and radon. Earlier experiments in animals strongly support the protective effect that is apparent in humans. Also, experimental reports from invertebrates kept in radiation-deficient conditions suggest that ionizing radiation is essential for optimal growth and development. The combined evidence points to the presence of no-adverse-effect thresholds and of hormesis or beneficial effects at doses below those thresholds. Furthermore, according to the geological record, the high background radiation under which life first evolved has progressively attenuated up to the present. Thus it is intriguing to postulate that modern humans may live under conditions of partial deficiency of ionizing radiation; low doses of ionizing radiation may likely function as inducers of repair and detoxification mechanisms, much as low-level antigenic challenges are responsible for enhanced immune competence. This hypothesis runs contrary to the prevailing consensus of regulatory default assumptions, which negate the possibility of no-effect thresholds for agents that are carcinogenic at certain levels of exposure. Still, those are dogmatic policy assumptions without scientific or even empirical justification, whereas the hypothesis advanced here has consistent observational and experimental support. The implication is that a partial deficiency of ionizing radiation could be remedied by a safe supplementation, possibly through dietary means. Dose-response data from studies of nuclear workers and populations subjected to unusual exposures suggest that safe supplementation with about 0.4 cGy/mo would be beneficial and conservative.

Animals↗