Effect of mass, oxidation state and duration of chronic ingestion on plutonium absorption in fed rats

The effects of time, mass and oxidation state on plutonium gastrointestinal absorption and tooth adsorption were studied during and after chronic ingestion of plutonium-238 (IV) or (VI) (1.55-15.60 kBq/ml) in 6.5 mM bicarbonate medium by fed rats via drinking water for 8 days to 3 months. Animals were killed during the ingestion to follow the kinetics of whole-body storage and clearance of plutonium. At 1.55 kBq/ml the amount of plutonium retained in the skeleton increased continuously during the 85 days of ingestion and reached a plateau thereafter. This plutonium retention was therefore dependent on the total mass administered but not proportional to this mass, as the fraction of administered plutonium retained decreased during the first 22 days of ingestion and then stabilized. This is reflected by the gastrointestinal transfer (f1), which had risen to (3.80 +/- 0.82) x 10(-5) on Day 3 of ingestion and then decreased to a stabilized value of (1.07 +/- 0.06) x 10(-5) from Day 30 to the end of the ingestion period. In the liver, the amount of plutonium retained reached a plateau, which lasted from Day 30 to the end of ingestion. The kidneys and spleen were also found to be retention sites. By Day 3 of ingestion, for a mass ingested of 5 x 10(-7) g/kg of body mass, the maximum mean value of f1 we found was smaller than the 10(-4) recommended by ICRP Report 30. The oxidation state had no effect on f1. Large plutonium deposition was observed on the teeth. For both oxidation states (IV) and (VI), about 0.10% of the administered dose was deposited on the teeth after 3 days of ingestion, whatever the plutonium concentration administered. However, whereas the amount of plutonium (IV) deposited did not change throughout the ingestion period, tooth deposition of plutonium (VI) decreased.     

The Gastrointestinal Absorption of Organically Bound Forms of Plutonium in Fed and Fasted Hamsters

Summary

Values of about 0·005–0·01 per cent were obtained for the absorption in fed hamsters of plutonium ingested as Pu⁴⁺ citrate, isocitrate, phytate and malate complexes and Pu³⁺ ascorbate compared with about 0·003–0·004 per cent for Pu⁴⁺ nitrate. Replacing drinking water with tea did not affect the result for Pu⁴⁺ nitrate. Fasting hamsters for 8 h before the administration of plutonium citrate increased absorption to 0·1–0·2 per cent. An extra period of fasting for 4 h after administration did not lead to a further increase in absorption. Similar values were also obtained when plutonium citrate was administered after a 24 h fast, followed either by immediate access to food or a further 4 h fast. In hamsters fasted for 24 h before administration of either Pu³⁺ ascorbate or Pu⁴⁺ nitrate, about 6–7 per cent of the ingested plutonium was retained in the gastrointestinal tract after one week. At three weeks after ingestion of Pu³⁺ ascorbate, gastrointestinal retention had fallen 100-fold without an increase in absorption.     

The Induction by 239Pu of Myeloid Leukaemia and Osteosarcoma in Female CBA Mice

Summary

Plutonium-239 was injected into 12-week-old female CBA/H mice in the range 1·85–18·5 kBq kg^?1 either as a single injection or as 16 injections spaced at 3·5 day intervals over eight weeks. There was a highly significant increase in the yield of fully developed osteosarcomas with increased amounts of ²³⁹Pu for both modes of injection. Osteosarcomas too small to be diagnosed radiographically were also seen in many bones and small but significant yields of myeloid leukaemia were seen in animals given plutonium. Although more myeloid leukaemia was seen in the mice given plutonium in divided amounts than in those given the plutonium in a single injection it could not be shown that multiple injection significantly affected the yield of either late effect.     

The Radiolysis of Dilute Solutions of Lysozyme

Summary

Pulse radiolysis was used for the study of transients formed from lysozyme solutions. Reactions of these transients with cysteine and oxygen were analysed kinetically. The rate constant for the reaction of lysozyme with e^?_aq was 5·2 × 10¹⁰ M^?1 sec^?1 and for lysozyme with OH was 3·1 × 10¹⁰ M^?1 sec^?1. For the reaction of the lysozyme transient (λ_max 400 mμ) with cysteine and oxygen, the rate constants were 4·1 × 10⁶ M^?1 sec^?1 and 3·38 × 10⁸ M^?1 sec^?1 respectively. The corresponding figures for the lysozyme transient (λ_max 310 mμ) were 4·6 × 10⁸ M^?1 sec^?1 and 1·6 × 10⁸ M^?1 sec^?1. These data are correlated with those obtained from steady-state radiolysis and elucidate an aspect of the known radiobiological oxygen effect.     

Interactions of Thiyl Free Radicals with Oxygen: A Pulse Radiolysis Study

Summary

A pulse radiolysis study of glutathione in aqueous solution at pH 5·5 containing N₂O/O₂ mixtures at various ratios indicates that oxygen rapidly adds to the thiyl glutathione radical yielding a transient absorption, with a maximum at 540 nm, whose characteristics appear to be compatible with assignment to the GSOO^· radical. The reaction appears to be an equilibrium whose kinetic constants have been estimated (k_f = 2·0 × 10⁹ dm³ mol^?1 s^?1, k_b = 6·2 × 10⁵ s^?1). Evidence for electron transfer from ascorbate to the GSOO^· radical has been obtained and the respective rate constant has been determined to be 1·75 ± 0·15 × 10⁸ dm³ mol^?1 s^?1.     

Association for Radiation Research/Netherlands Radiobiological Society

Summary

The kinetics of pulse radiolytically induced intramolecular radical transformations: Trp/N^·→Tyr/O^·, Tyr/O^·→Trp/N^·, Met/S∴Br→Trp/N^· and Met/S∴Br→Tyr/O^· has been investigated at various pH levels and temperatures in model peptides: Trp-(Pro)_n-Tyr, Trp-(Gly)_n-Tyr, Trp-(Pro)_n-Met (n = 0–3), Tyr-Phe-Met-Arg-Phe-NH₂·2AcOH, Met⁵-enkephaline and [d-Ala]²Met⁵-enkephaline. The rate constants of the Trp/N^·→Tyr/O^· transformation at pH 8 were found to decrease exponentially with the distance between Trp and Tyr in the proline peptides, while in the glycine peptides the rate of the transformation is less dependent on the number of bridging glycine residues. The activation energies determined fall into the range 10–20 kJ mol^?1 irrespective of: (i) the ionization state of tryptophyl radical and tyrosine, (ii) type of bridging amino acids, and (iii) reversal of the direction of the electron transfer upon tyrosine OH group ionization. The activation entropies at 298 K for the peptides of the glycine and proline series are negative and rather high, and fall into the relatively narrow range of ?90 to ?140 J mol^?1 deg^?1. These activation parameters seem to indicate that a tunnelling mechanism is involved in the electron transfer between strictly oriented aromatic moieties of Trp and Tyr. The variation of the activation parameters with average separation distance in the case of Trp-(Pro)_n-Tyr shows a predominance of the electronic factor over the nuclear in determining the distance dependence of the electron transfer rate. The intramolecular Met/S∴Br→Tyr/O^· transfer proceeds with the rate constant of 1·1 × 10⁵ s^?1 in Met⁵-enkephaline and 5·7 × 10⁴ s^?1 in [d-Ala]²Met⁵-enkephaline. The activation parameters for this transformation E_a = 30 kJ mol^?1 and ΔS⁴₂₉₈ = ?62 J mol^?1 deg^?1 are close to those of the Trp/N^·→Tyr/O^· transformation, suggesting a similar mechanism for the electron transfer.     

The Reactions of the Hydroxymethyl Radical with 1,3-dimethyluracil and 1,3-dimethylthymine

Summary

Hydroxymethyl radicals ·CH₂OH, generated by the radiolysis of methanol (0·5 mol dm^?3) in N₂O-saturated aqueous solutions, were reacted with 1,3-dimethyluracil or 1,3-dimethylthymine (10^?3) mol dm^?3). The products were identified and their G values determined. It has been concluded that in 1,3-dimethyluracil ·CH₂OH attack occurs only at C(6) while in 1,3-dimethylthymine there is partitioning between addition (two-thirds) and H-abstraction from the C(5)-methyl group (one-third). A rate constant for CH₂OH addition to 1,3-dimethyluracil of about 10⁴ dm³ mol^?1 s^?1 is estimated. Complexities that may arise in the radiolysis of pyrimidines such as 1,3-dimethylthymine, apparently as a consequence of the formation of 5-alkylidenepyrimidines, are discussed. A value of 0·15 has been estimated for the disproportionation/combination ratio for the hydroxymethyl radical self-termination reaction.     

One-electron Reduction of 8-hydroxy-5-deazaisoalloxazine in Aqueous Solution: A Pulse Radiolysis Study

Summary

The one-electron reduction of 8-hydroxy-5-deazaisoalloxazine (HMDI) has been studied in aqueous solution in the acidity range pH0 to 13 using the reducing species CO₂·^?, e^?_aq and (CH₃)₂COH radicals. The spectral and other properties of the HMDI radicals were found to be independent of the reductant used. Four protolytic forms of the radical were distinguished with associated pK_a values of 2·3 ± 0·3, 6·0 ± 0·3 and 10·1 ± 0·3.     

X-ray Induced Free Radicals in Single Crystals of N-acetyl-L-leucine

Summary

Double-stranded DNA from calf thymus was irradiated in the presence of bovine serum albumin (BSA) at a ratio of 1:10 by mass under air, N₂ or N₂O, with and without ethanol, tert-butanol or isopropanol in 10^?2 mol dm^?3 sodium phosphate buffer, pH 7·0. The irradiated solutions were analysed by a nitrocellulose filter assay and by high-performance liquid gel chromatography. The results show that OH^· radicals as well as hydrated electrons induce protein—DNA crosslinks. Further, alcohol radicals react with BSA producing protein radicals which become crosslinked to DNA. If OH radicals are scavenged by alcohol, strand breakage of DNA does not occur.     

Temporal and anatomical variations of brain water apparent diffusion coefficient in perinatal cerebral hypoxic-ischemic injury: Relationships to cerebral energy metabolism

Cerebral apparent diffusion coefficients {ADCs) were determined in nine newborn piglets before and for 48 h after transient hypoxia-ischemia. Phosphorus MRS revealed severely reduced cerebral energy metabolism during the insult and an apparently complete recovery 2 h after resuscitation commenced. At this time, mean ADC over the imaging slice (ADC_global) was 0.88 (0.04) × 10^{? 9} m² · s^{? 1} (mean (SD}), which was close to the baseline value of 0.92 (0.4) × 10^{? 9} m² · s^{? 1}. In seven of the animals, a “secondary” failure of energy metabolism then evolved, accompanied by a decline in ADC_global to 0.64 (0.17) × 10^{? 9} m² · s^{? 1} at 46 h postresuscitation (P < 0.001 versus baseline). For these seven animals, ADC_global correlated linearly with the concentration ratio [phosphocreatine (PCr)][inorganic phosphate (Pi)] (0.94 r < 0.99; P > 0.001). A nonlinear relationship was demonstrated between ADC_global, and the concentration ratio [nucleotide triphosphate (NTP)]/ [Pi + PCr + 3 NTP]. The ADC reduction commenced in the parasagittal cortex before spreading in a characteristic pattern throughout the brain. ADC seems to be closely related to cerebral energy status and shows considerable potential for the assessment of hypoxic-ischemic injury in the newborn brain.     

Chemical Properties of Water-soluble Porphyrins. 5. Reactions of Some Manganese (III) Porphyrins with the Superoxide and Other Reducing Radicals

Summary

Solution properties of three manganese porphyrins, in monomeric form, were investigated. These were the ‘picket-fence-like’ porphyrin Mn(III)-α,α,α,β-tetra-ortho(N-methylisonicotinamidophenyl)porphyrin (Mn(III)PFP) and two ‘planar unhindered’ porphyrins, the Mn(III)TMPyP (tetrakis (4-N-methylpyridyl)porphyrin) and Mn(III)TAP (tetra(4-NNN-trimethyl-anilinium)porphyrin). The porphyrin properties studied were: the absorption spectra in their manganic and manganous forms; acid/base properties of the aquo complexes; the effect of potential axial ligands (up to a concentration of 0·1 mol dm^?3) and their one electron reduction potentials. Knowing these properties, the reaction of the Mn(III) porphyrins with the superoxide radical and other reducing radicals were studied using the pulse radiolysis technique. The second-order reaction rate constant of O^?₂ with the Mn(III) porphyrins, which governs the catalytic efficiency of the metalloporphyrins upon the disproportionation of the superoxide radical, was 5·1 × 10⁷ to 4·0 × 10⁵ dm³ mol^?1s^?1, depending on the pH and the nature of the metalloporphyrin. These values are at least one order of magnitude lower than found for Fe(III)TMPyP. One electron reduction of the three Mn(III) porphyrins by e^?_aq, CO^?₂, CH₂OH and (CH₃)₂COH had similar second-order rate constants (10⁹-10¹⁰ dm³ mol^?1 s^?1). That for (CH₃)₂(CH₂)COH was about 10⁵ dm³ mol^?1 s^?1. Reduction in all cases produced the corresponding Mn(II) porphyrin and no intermediate was found. The oxidation reaction of the Mn(II) porphyrins by O^?₂ was approximately two orders of magnitude faster when compared to the reduction of Mn(III) porphyrins with the same radical. Since the reactivities of O^?₂ towards the three manganese (III) compounds follow their reduction potentials, it is suggested that these reactions are governed by an outer-sphere mechanism. This suggestion is corroborated by the finding that water molecules acting as axial ligands, in these aqueous solution systems, are not replaced by another potential ligand when the latter is in the concentration range of 100 mm or less.     

One-electron Reduction of 5-deazalumiflavin in Aqueous Solution: A Pulse Radiolysis Study

Summary

The one-electron reduction of 5-deazalumiflavin has been studied in aqueous solution in the acidity range H₀ = ?1 to pH 13 using the reducing species CO₂^?, e^?_aq and (CH₃)₂?OH radicals. The spectral and other properties of the deazaflavin radicals formed were found to be independent of the reductant used. Four protolytic forms of the radical were distinguished with associated pK_a values of 1·3 ± 0·3, 6·0 ± 0·3 and 10·7 ± 0·3.     

Age-dependent Variation of Zinc-65 Metabolism in LACA Mice

Summary

Mice were gavaged with zinc-65 solution, 8·6–19·3 kBq per mouse, and the whole-body retention and organ content of zinc-65 were measured at different times after administration. The age-dependence of the fractional absorption of zinc-65 from the gastrointesinal tract (f₁), the endogenous faecal excretion fraction of zinc-65 (EFEF), tissue distribution and whole-body retention were determined. The f₁ values obtained were 0·86 ± 0·15, 0·64 ± 0·11, 0·52 ± 0·07 and 0·39 ± 0·02 in suckling, adolescent, young adult and older mice, respectively. The EFEF values determined were 0·083 ± 0·008, 0·099 ± 0·004, 0·122 ± 0·018 and 0·144 ± 0·005 of intraperitoneally injected zinc-65 in suckling, adolescent, young adult and older mice at administration. Zinc-65 mainly distributed in the liver, muscle, lung, kidneys and bone. In some tissues, there was an inverse relationship between the relative content of gavaged zinc-65 and the animal's age at administration. The whole-body biological half-lives of zinc-65 increased with animal age. The influence of the age-dependent variation of zinc-65 metabolism on internal dose and on radiation protection is discussed.     

Subject Index

Summary

Using conductivity detection, pulse radiolysis experiments showed that solvent protonation of the electron adducts of cytosine, 5-methyl cytosine and 2′-deoxycytidine occurs with rate constants k ≥ 2 × 10⁴M^?1s^?1. The protonated electron adducts transfer an electron to p-nitroactetophenone (PNAP) with rate constants ranging from 3·5×10⁹ to 5·3·10⁹M^?1s^?1. The transfer is quantitative (G = 2·7), as shown by conductometric and spectroscopic measurements. In the presence of O₂ no electron transfer to O₂ takes place, implying that O₂ adds to the protonated electron adduct radicals.

No electron transfer from the H- and OH-adducts of the cytosine derivatives, either to PNAP or to O₂, takes place near neutral pH. It is suggested that the differences in the reaction behaviour of the H-adduct radicals and the protonated electron adduct radicals towards PNAP can be accounted for if different radicals are formed by H-addition and protonation of the electron adduct. The H atoms most probably add to the C-5-C-6 double bonds, whereas the electron adducts are protonated at N-3 and/or 0-2.     

Rates for Repair of pBR 322 DNA Radicals by Thiols as Measured by the Gas Explosion Technique: Evidence that Counter-ion Condensation and Co-ion Depletion are Significant at Physiological Ionic Strength

Summary

Rates of repair of pBR 322 plasmid DNA radicals by thiols of varying net charge (Z) at pH 7 and physiological ionic strength were measured using the oxygen explosion technique. The extent of conversion of supercoiled to relaxed circular plasmid was measured by HPLC as a function of the time of oxygen exposure before or after irradiation, the time-courses being fitted by a pseudo-first-order kinetic expression with k₁ = k₂[RSH]. Values of k₂ (M^?1 s^?1) were: 2·1 × 10⁵ (GSH, Z = ?1), 1·4 × 10⁶ (2-mercaptoethanol, Z = 0), 1·2 × 10⁷ (cysteamine, Z = +1), 6·6 × 10⁷ (WR-1065 or N-(2-mercaptoethyl)-1,3-diaminopropane, Z = +2). The approximately 6-fold increase in rate with each unit increase in Z is attributed to concentration of cationic thiols near DNA as a consequence of counter-ion condensation and reduced levels of anionic thiols near DNA owing to co-ion depletion. The results are quantitatively consistent with chemical repair as a significant mechanism for radioprotection of cells by neutral and cationic thiols under aerobic conditions, but indicate that repair by GSH will compete effectively with oxygen only at low oxygen tension.     

High dose Nitrate ingestion does not improve 40 km cycling time trial performance in trained cyclists

ABSTRACT

This study evaluated the chronic effects of nitrate (NO₃^?) ingestion over three days, on 40 km TT performance in 11trained cyclists (VO_2max: 60.8 ± 7.4 ml.kg^?1.min^?1; age: 36 ± 9 years; height: 1.80 ± 0.06 m; body mass: 87.2 ± 12.0 kg). Utilising a double-blind randomised cross-over design, participants completed three 40 km TT on a Velotron® ergometer following the ingestion of either a 140 ml of “BEET It sport®” NO₃^? shot containing 12.8 mmol or 800 mg of NO₃^?, a placebo drink or nothing (control). Performance, oxygen consumption (VO₂), blood bicarbonate (HCO3-), pH and lactate (BLa) and ratings of perceived exertion (RPE) were measured every 10 km throughout the TT. The present findings show that NO₃^? ingestion had no effect on TT performance (NO₃^?: 4098.0 ± 209.8 vs. Placebo: 4161.9 ± 263.3 s, p = 0.296, ES = 0.11), or VO₂ (p = 0.253, ES = 0.13). Similarly, blood lactate and RPE were also unaffected by the experimental conditions (p = 0.522, ES = 0.06; p = 0.085, ES = 0.30) respectively. Therefore, these results suggest that a high dose of NO₃^? over three days has limited efficacy as an ergogenic aid for 40 km TT cycling performance in trained cyclists.     

Effect of acute exercise-induced fatigue on maximal rate of heart rate increase during submaximal cycling

Different mathematical models were used to evaluate if the maximal rate of heart rate (HR) increase (rHRI) was related to reductions in exercise performance resulting from acute fatigue. Fourteen triathletes completed testing before and after a 2-h run. rHRI was assessed during 5 min of 100-W cycling and a sigmoidal (rHRI_sig) and exponential (rHRI_exp) model were applied. Exercise performance was assessed using a 5-min cycling time-trial. The run elicited reductions in time-trial performance (1.34 ± 0.19 to 1.25 ± 0.18 kJ · kg^?1, P < 0.001), rHRI_sig (2.25 ± 1.0 to 1.14 ± 0.7 beats · min^?1 · s^?1, P < 0.001) and rHRI_exp (3.79 ± 2.07 to 1.98 ± 1.05 beats · min^?1 · s^?1, P = 0.001), and increased pre-exercise HR (73.0 ± 8.4 to 90.5 ± 11.4 beats · min^?1, P < 0.001). Pre-post run difference in time-trial performance was related to difference in rHRI_sig (r = 0.58, P = 0.04 and r = 0.75, P = 0.003) but not rHRI_exp (r = ?0.04, P = 0.9 and r = 0.27, P = 0.4) when controlling for differences in pre-exercise and steady-state HR. rHRI_sig was reduced following acute exercise-induced fatigue, and correlated with difference in performance.     

Chromosomal Abnormalities Induced by Iodine-125 in Mouse Germ Cells

Summary

Swiss albino male mice were injected intraperitoneally with 0, 185, 370 or 555 kBq (0, 5, 10 or 15 µCi) of iodine-125 (¹²⁵I). All the animals were killed on the sixtieth day and chromosomal aberrations were screened in spermatocytes at meiotic metaphase I. A significant increase in the percentage of chromosomal aberrations including translocations (0, 1·2, 1·8 and 2·3 per cent translocations in controls, 185, 370 and 555 kBq groups respectively) was recorded at all dose levels indicating the clatogenic effects of ¹²⁵I in mouse spermatocytes.     

Reactions of OH Radicals with Poly(U) in Deoxygenated Solutions: Sites of OH Radical Attack and the Kinetics of Base Release

Summary

Pulse radiolysis of N₂O-saturated solutions of poly(U) in the presence of tetranitromethane showed that 81 per cent of the radicals formed are reducing in nature. Using data from other sources it has been estimated that 70 per cent of the OH radicals add to the base at C(5) and 23 per cent at C(6) while only 7 per cent abstract an H-atom from the sugar moiety. To a large extent the C(5) OH adduct radicals attack the sugar moiety of poly(U) thereby inducing strand breakage and base release. G (base release) = 2·9 can be subdivided into three components: (a) immediate (20 per cent), (b) fast (50 per cent) and (c) slow (30 per cent). The immediate base release must occur either during the free-radical stage or as a result of the rapid (t_½ < 4 min at 0°C) decomposition of a diamagnetic product. The fast and the slow processes are only readily observable at elevated temperatures, e.g. at 50°C the half lives are 83 min and 26 h, respectively (E_a (fast) = 68 kJ mol^?1, E_a (slow) = 89 kJ mol^?1, A (fast) = 1·5 × 10⁷ s^?1, A (slow) = 1·9 × 10⁹ s^?1. It is concluded that there are three different types of sugar lesions giving rise to base release, structures for which are tentatively proposed.     

The influence of the b‐value combination on apparent diffusion coefficient based differentiation between malignant and benign tissue in cervical cancer

Purpose:

To analyze the influence of different b‐value combinations on apparent diffusion coefficient (ADC)‐based differentiation of known malignant and benign tissue in cervical cancer patients.

Materials and Methods:

A total of 35 patients with stage IB1, IB2, IIA cervical cancer underwent a 3.0T MRI scan prior to radical hysterectomy and pelvic lymph node dissection. Conventional T1‐ and T2‐weighted sequences and a diffusion‐weighted sequence (b = 0, 150, 500, 1000 seconds/mm²) were performed. Regions‐of‐interest (ROI) were drawn on ADC maps derived from five different b‐value combinations (0, 500; 0, 150, 500; 0, 1000; 0, 150, 500, 1000; 150, 500, 1000 seconds/mm²). The influence of the b‐value combination on ADC‐based differentiation of benign and malignant tissue was analyzed using receiver‐operating‐characteristics curves.

Results:

For all b‐value combinations, ADCs were significantly lower (P < 0.001) in cervical malignancies (1.15 ± 0.21·10^?3; 1.10 ± 0.21·10^?3; 0.97 ± 0.18·10^?3; 0.97 ± 0.23·10^?3 and 0.85 ± 0.18·10^?3 mm²/second respectively to the aforementioned b‐value combinations) than in benign cervix (2.08 ± 0.31·10^?3; 2.00 ± 0.29·10^?3; 1.62 ± 0.23·10^?3; 1.54 ± 0.21·10^?3 and 1.42 ± 0.22·10^?3 mm²/second respectively). The diagnostic accuracy was high for all b‐value combinations and without statistical differences between the combinations.

Conclusion:

ADC‐based differentiation of benign from malignant cervical tissue is independent of the tested b‐value combinations. The results support the inclusion and possible pooling of studies using different b‐value combinations in meta‐analyses on ADC‐based tissue differentiation in cervical cancer. J. Magn. Reson. Imaging 2010;32:376–382. © 2010 Wiley‐Liss, Inc.