Einar Sagstuen

EPR dosimetric properties of formates.

As a part of a program to develop an electron paramagnetic resonance (EPR) dosimeter suited for clinical use (doses in the cGy range), polycrystalline samples of lithium formate monohydrate (HCO2Li.H2O), magnesium formate dihydrate (C2H2O4Mg.2H2O), and calcium formate (C2H2O4Ca) have been examined. L-Alanine was included for comparison and reference. Samples were irradiated with 60Co gamma-rays and 60-220 kV X-rays. The dosimeter response was assessed using the peak-to-peak amplitude of the first-derivative EPR spectrum. Dose-response curves for the 60Co gamma-irradiated samples were constructed, and the dependences of the response on the photon energy, microwave power, and modulation amplitude were studied. Stability of the irradiation products upon storage (signal fading) was also investigated. Lithium formate monohydrate is by far the best candidate of the tested formates, suitable for measuring doses down to approximately 0.1 Gy. Lithium formate monohydrate is more sensitive than alanine by a factor of 5.6-6.8 in the tested photon energy range, it exhibits no zero-dose signal and shows a linear dose response in the dose range from 0.2 to 1000 Gy. Its EPR signal was found unchanged in shape and intensity 1 week after irradiation to 10 Gy. Various less favorable properties rendered the other formates generally unsuitable, although calcium formate exhibits some interesting EPR dosimetric properties.

Alanine Radicals, Part 3: Properties of the Components Contributing to the EPR Spectrum of X-Irradiated Alanine Dosimeters

Abstract Malinen, E., Heydari, M. Z., Sagstuen, E. and Hole, E. O. Alanine Radicals, Part 3: Properties of the Components Contributing to the EPR Spectrum of X-Irradiated Alanine Dosimeters. Radiat. Res. 159, 23–32 (2003). The amino acid l-α-alanine has attracted considerable interest for use in radiation dosimetry and has been formally accepted as a secondary standard for high-dose and transfer dosimetry. Recent results have shown that the alanine EPR spectrum consists of contributions from three different radicals. A set of benchmark spectra describing the essential spectral features of these three radical components was used for reconstructions of the experimental spectra. In the present work, these basis spectra have been used to investigate the differential effects of variations in radiation doses and microwave power, as well as the dependence upon temperature annealing and UV illumination. The results presented here, based solely on relatively low-energy (60–80 keV) X rays, indicate that the three components behave very similarly with respect to radiation dose at room temperature. However, with respect to the thermal annealing/fading behavior and microwave power saturation properties, the three species behave significantly differently. It is concluded that even if it is now realized that three different radicals contribute to the composite EPR alanine spectrum, this has a minor impact on the established protocols for present-day applications (high-dose) of EPR/alanine dosimetry. However, some care should be exercised when e.g. constructing calibration curves, since fading and power saturation behavior may vary over the dose range in question. New results from UV-illumination experiments suggest a possible procedure for experimental spectral separation of the EPR signals due to the three radicals.

ESR study of the guanine cation

It has been proposed that the primary direct radiation damage products in DNA are guanine cations and thymine anions. Experiments reported here characterize a guanine cation observed in a single crystal of guanine:HCl:H2O. ESR experiments were performed by x‐irradiating and observing the crystals at 15 K. Spectral parameters for the cation include N3 and N10 hyperfine couplings, a C8–Hα hyperfine coupling, and two small exchangeable couplings presumably from the N10 protons. The computed spin densities of ρ(N3)=0.283, ρ(N10)=0.168, and ρ(C8)=0.182 agree nicely with those observed for the guanine cation in DNA. In the single crystal the native molecule is protonated at N7. It is proposed that once the native molecule is oxidized it rapidly deprotonates at N7 to form the cation observed.

The solid-state radiation chemistry of simple amino acids, revisited.

Abstract Sagstuen, E., Sanderud, A. and Hole, E. O., The Solid-State Radiation Chemistry of Simple Amino Acids, Revisited. Radiat. Res. 162, 112–119 (2004). The solid-state radiation-induced free radical formation in simple amino acids like α-glycine (gly) and l-α-alanine (ala) has been the subject of investigations by EPR spectroscopy since the late 1950s. The EPR spectra from crystals of gly and ala generally are very complex due to the simultaneous trapping of several free radicals regardless of irradiation and observation temperatures. Untangling these complex spectra is necessary for understanding the mechanisms for the solid-state radiation chemistry of amino acids. Recently, radical formation in gly and ala after room-temperature irradiation has been reinvestigated in our laboratories using X-, K- and Q-band EPR and ENDOR spectroscopy, combined with the ENDOR-induced EPR (EIE) techniques as well as single-crystal and powder EPR and ENDOR spectrum simulations. Several new radical products have been detected and characterized, most prominently the gly species H2N − C·H − COOH and the ala species H3+N − C·(CH3) − COO− and H2N − C·(CH3) − COOH. A short description of these radicals is given, and an overview of the solid-state radiation chemistry of the simple amino acids is presented, based on a review of the literature combined with these recent experimental results.

ESR and ENDOR study of the guanine cation: Secondary product in 5’‐dGMP

Previous ESR studies of x‐irradiated single crystals of 2’‐deoxyguanosine‐5’‐monophosphate have indicated the presence of a radical thought to be formed by deprotonation of a primary base cation at N1. In this communication are reported some results of detailed ESR and ENDOR experiments at 10 K conflicting with the above results. One of the radicals detected exhibited two α‐proton type couplings. The data analysis shows that one coupling is due to the exchangeable proton of the extra‐annular NH2 group, while the other is due to the proton bonded at C8. The experimental spin densities were ρ(N10)=0.33, and ρ(C8)=0.18. The results agree reasonably well with the INDO calculated spin density distribution of a radical formed by deprotonation at N10 of a primary cation radical. The radical is stable on warming to about 200 K where it anneals rapidly.

Dosimetry by ESR spectroscopy following a radiation accident

On 2 September, 1982, one of the employees of the gamma-irradiation facility at The Institute for Energy and Technology (Kjeller, Norway) entered the irradiation cell with a 65.7-kCi 60Co source in unshielded position. The victim received an unknown radiation dose and died after 13 days. Using electron-spin resonance spectroscopy (ESR), the radiation dose in this accident was subsequently determined based on the production of long-lived free radicals in nitroglycerol tablets carried by the operator during accident. He used nitroglycerol for heart problems and free radicals are easily formed and trapped in sugar which is the main component of the tablets. Calibration experiments were carried out and the dose given to the tablets during the accident was determined to be 39 Gy. Phantom experiments based on this result indicate an average whole-body dose in the accident of 22.5 Gy.

Radical formation in X-irradiated single crystals of guanine hydrochloride monohydrate. II. ESR and ENDOR in the range 10-77 K.

In a study of guanine.HCl.H2O (Gm) single crystals X-irradiated at temperatures between 10 and 77 K, three radical species were found and characterized by ESR and ENDOR spectroscopy. All three are primary products in that they were present immediately following irradiation at T less than 10 K. Radical I, which apparently can exist in two slightly different conformations, was identified as the product of electron gain by the parent molecule and subsequent protonation at O6. Radical I decayed only after warming the crystals beyond 250 K. Radical II was the guanine cation previously reported (D. M. Close, E. Sagstuen, and W. H. Nelson, J. Chem. Phys. 82, 4386 (1985)); however, ENDOR data are reported here which confirm the previous results. The guanine cation in Gm resulted from electron loss from the parent and subsequent deprotonation at N7. It is proposed that Radical III results from OH attack at C8 of the parent molecule, followed by rupture of the C8-N9 bond and ring opening. The OH radicals thought to produce Radical III result from electron loss by the cocrystallized water molecules. The reaction leading to Radical III, unusual in solid-state radiation chemistry, is thought to be mediated by the specific hydrogen bonding network in this crystal.

Alanine Radicals, Part 4: Relative Amounts of Radical Species in Alanine Dosimeters after Exposure to 6–19 MeV Electrons and 10 kV–15 MV Photons

Abstract Malinen, E., Hult, E. A., Hole, E. O. and Sagstuen, E. Alanine Radicals, Part 4: Relative Amounts of Radical Species in Alanine Dosimeters after Exposure to 6–19 MeV Electrons and 10 kV–15 MV Photons. Radiat. Res. 159, 149–153 (2003). The amino acid l-α-alanine can be used for high-precision dosimetry over a wide dose range, using EPR spectroscopy for monitoring radical concentrations. It is important, however, to understand the underlying composition of the observed EPR spectrum. In previous work, it was shown that the EPR signal from irradiated alanine consists of at least three different radical species, with the relative importance of each of these being almost independent of absorbed dose. However, it was not known whether the relative importance of each radical is independent of the radiation quality responsible for the EPR signal. In the present work, the relative contributions of the different radical species to the total EPR signal from alanine dosimeters irradiated with 6–19 MeV electrons and 10 kV–15 MV photons at a dose of 10 Gy were examined. By spectrum reconstruction using benchmark spectra generated from a simulation procedure, the relative amounts of the three different radical species were shown to be virtually independent of these radiation beam qualities.

The energy dependence of lithium formate and alanine EPR dosimeters for medium energy x rays

PURPOSE To perform a systematic investigation of the energy dependence of alanine and lilthium formate EPR dosimeters for medium energy x rays. METHODS Lithium formate and alanine EPR dosimeters were exposed to eight different x-ray beam qualities, with nominal potentials ranging from 50 to 200 kV. Following ionometry based on standards of absorbed dose to water, the dosimeters were given two different doses of approximately 3 and 6 Gy for each radiation quality, with three dosimeters for each dose. A reference series was also irradiated to three different dose levels at a 60Co unit. The dose to water energy response, that is, the dosimeter reading per absorbed dose to water relative to that for 60Co gamma-rays, was estimated for each beam quality. In addition, the energy response was calculated by Monte Carlo simulations and compared to the experimental energy response. RESULTS The experimental energy response estimates ranged from 0.89 to 0.94 and from 0.68 to 0.90 for lithium formate and alanine, respectively. The uncertainties in the experimental energy response estimates were typically 3%. The relative effectiveness, that is, the ratio of the experimental energy response to that following Monte Carlo simulations was, on average, 0.96 and 0.94 for lithium formate and alanine, respectively. CONCLUSIONS This work shows that lithium formate dosimeters are less dependent on x-ray energy than alanine. Furthermore, as the relative effectiveness for both lithium formate and alanine were systematically less than unity, the yield of radiation-induced radicals is decreased following x-irradiation compared to irradiation with 60Co y-rays.

A simple method for estimating dose uncertainty in ESR/alanine dosimetry

Abstract ESR/alanine dosimetry is widely used as a reference, transfer and routine standard dosimetry system. In order to use it as a reliable standard, or in every situation where a high degree of accuracy is needed, the calculation of the absolute dose uncertainty is required. Even though general guides for estimating dose uncertainties are available, the actual calculation may be rather complicated. In this paper, an analytical expression for the dose uncertainty for the ESR/alanine dosimetry system is presented, and shown to be rather simple to use. The treatment is valid for doses below ca. 103 Gy. An alternative procedure should be followed if the calibration dose uncertainties are very varying, e.g. when the calibration dose range is wide. This procedure, the so-called effective variance method [Orear, J. (1982) Am. J. Phys. 50, 912], is described. Both methods are supplied with one numerical example. Suggestions on obtaining calibration curve parameters and their uncertainties, are emphasized.