Delayed effects of acute radiation injuries by radioactive carbon (14C-glycine)

A study was made of late biological effects of radioactive carbon (14C-glycine) applied in acute doses. The course of radiation sickness, at its acute stage, is similar to that of acute radiation sickness caused by external gamma-irradiation. The recovery is slow, and the disease becomes chronic exhibiting metabolism disturbances and early death of animals. Radioactive carbon has a pronounced blastomogenic action.     

Metabolism of phytol-U-14C and phytanic acid-U-14C in the rat

The metabolism of uniformly-labeled (14)C-phytol, (14)C-phytenic acid, and (14)C-phytanic acid was studied in the rat. Conversion of both phytol and phytenic acid to phytanic acid was demonstrated. Tracer doses of phytol-U-(14)C given orally were well absorbed (30-66%), and approximately 30% of the absorbed dose was converted to (14)CO(2) in 18 hr. After intravenous injection, 20% appeared in (14)CO(2) in 4 hr. Phytanic acid-U-(14)C given intravenously was oxidized at a comparable rate (22-37% in 4 hr) and was as rapidly oxidized as palmitic acid-1-(14)C (21% in 4 hr). Metabolism of these substrates was also studied in rats previously maintained on a diet containing 5% phytol by weight, which causes accumulation of phytanic acid, phytenic acid, and, to a lesser extent, phytol in blood and tissues. Despite the large body pools of preformed, unlabeled substrate in these animals, the fraction of an administered dose of phytol-U-(14)C or phytanic acid-U-(14)C converted to (14)CO(2) was not significantly diminished. These studies indicate that the rat has an appreciable capacity to degrade the highly branched carbon skeleton of phytol and its derivatives. Twenty-four hours after administration of phytol-U-(14)C, the lipid radioactivity remaining in the body was widely distributed among the tissues, highest concentrations being found in liver and adipose tissue. Four hours after intravenous administration of phytanic acid-U-(14)C, all of the major lipid classes in the liver contained radioactivity, most in triglycerides and phospholipids and least in cholesterol esters and lower glycerides. There was no demonstrable incorporation of mevalonate-2-(14)C or acetate-1-(14)C into liver phytanic acid when they were given intravenously to a rat previously fed phytol. Endogenous biosynthesis, if it occurs at all, must be extremely limited.     

A proposal for revision of the quality factor

As a result of recent radiobiological research it has become evident that the RBE of neurons can at low absorbed doses reach values that are substantially higher than the values of the quality factor (Q) currently adopted for radiation protection. There is theoretical and observational evidence that such high RBE values are the rule rather than the exception and that they apply to at least one radiation effect on humans. New values as well as different formulations are proposed for the factor that is employed in radiation protection to weight absorbed doses for their biological effectiveness.     

Effects of single and split doses of cobalt-60 gamma rays and 14 MeV neutrons on mouse stem cell spermatogonia

The long-term effects of ionizing radiation on male gonads may be the result of damage to spermatogonial stem cells. Doses of 10 cGy to 15 Gy (60)Co gamma rays or 10 cGy to 7 Gy 14 MeV neutrons were given to NMRI mice as single or split doses separated by a 24-h interval. The ratios of haploid spermatids/2c cells and the coefficients of variation of DNA histogram peaks as measures of both the cytocidal and the clastogenic actions of radiation were analyzed by DNA flow cytometry after DAPI staining. The coefficient of variation is not only a statistical examination of the data but is also used here as a measure of residual damage to DNA (i.e. a biological dosimeter). Testicular histology was examined in parallel. At 70 days after irradiation, the relative biological effectiveness for neutrons at 50% survival of spermatogonial stem cells was 3.6 for single doses and 2.8 for split doses. The average coefficient of variation of unirradiated controls of elongated spermatids was doubled when stem cells were irradiated with single doses of approximately 14 Gy (60)Co gamma rays or 3 Gy neutrons and observed 70 days later. Split doses of (60)Co gamma rays were more effective than single doses, doubling DNA dispersion at 7 Gy. No fractionation effect was found with neutrons with coefficients of variation.     

Sunflower germination and growth behavior under various gamma radiation absorbed doses

Gamma radiation, various absorbed doses (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5 krad) effects were evaluated on sunflower (Helianthus annus. L.) germination and growth characteristics. Sunflower healthy seeds were exposed to gamma radiation source Co⁶⁰ at nuclear institute for food and agriculture and exposed seeds were grown under controlled laboratory conditions. In comparison to control, gamma radiation absorbed doses affected the measured response positively i.e., radical length, plumule length, number of roots, seedling fresh weight, seedling dry weight, germination percentage, time of germination and diameter of hypocotyl of sunflower enhanced up to 83.15%, 70.32%, 73.03%, 4.80%, 3.26%, 72.0%, ? 18.88% and 12.58%, respectively. The time of germination, fresh weight and percent moisture contents enhanced insignificantly, however, the response was higher than control. All gamma radiation absorbed doses showed a stimulatory effect on sunflower germination and seedling growth characteristics. The low gamma radiation absorbed doses were found to be more effective versus higher doses for enhancing the germination and growth characteristics of sunflower. In view of positive effect of gamma radiation of sunflower germination and growth characteristics, it is concluded that this techniques could possibly be used for the enhancement of germination, growth and ultimately yield in sunflower in areas where germination is low due to unfavorable conditions.     

Biosynthetic labeling with 32P: Radiation damage to mammalian cells

Theoretical calculations showed that biosynthetic radiolabeling of cells using typical concentrations of ³²P (1 mCi/ml) resulted in high radiation doses (200–500 rad/h) being absorbed by the cells. Subsequent investigations with a mouse myelomonocytic leukemia cell line (WEHI-3B(D⁺)) showed significant loss of replicative ability during brief (less than 1 h) exposures to 1 mCi/ml of ³²P. Complete loss of cell replicative ability was found with isotopic doses less than 100 rad (i.e., 100 μCi/ml for 5 h). Experiments employing a less radiosensitive pre-B-cell line (18.81) revealed that significant loss of viability occurred during incubation with ³²P under identical conditions to those employed for the WEHI-3B(D⁺) cell line. Control experiments utilizing decayed batches of ³²P and physical separation of the isotope solution from the cells confirmed that the cytotoxicity was caused by radiation emission rather than the presence of toxic components in the isotopic solution. The radiation doses absorbed by cells biosynthetically labeled with ⁵⁹Fe, ³³P, ³⁵S, and ¹⁴C were calculated. Although significant levels of radiation can be absorbed ³²P was considerably more radiotoxic than the other isotopes. The results of calculations indicated that the judicious choice of container geometry could reduce the absorbed radiation dose from ³²P solutions. In particular the biosynthetic radiolabeling of cells in capillary tubes (diameter less than 1 mm) can reduce the absorbed rate to less than one-tenth of the dose received by cells suspended in Petri dishes or centrifuge tubes.     

Evaluation of radiation dose resulting from the ingestion of [3H]- and [14C]thymidine in the rat

Average doses to rat tissues from the ingestion of 2-[14C]thymidine were compared with those from methyl-[3H]thymidine or 6-[3H]thymidine. Among the three precursors, [14C]thymidine gave the highest dose to spleen and small intestine. The doses to other tissues from [14C]thymidine were almost the same or lower as compared with those from [3H]thymidine, irrespective of the 9 times higher beta-ray energy of 14C than that of 3H. In the case of [14C]thymidine, most of the dose was given by radioactivity incorporated into the organic tissue constituents (non-volatile radioactivity). In the case of [3H]thymidine, however, the dose contributions by non-volatile radioactivity were very small and the major contributions were rather from volatile radioactivity (3HHO), formed by degradation of [3H]thymidine. No significant difference in their total doses was found between the two [3H]precursors, but the dose from non-volatile radioactivity alone was 2-3 times higher with methyl-[3H]thymidine than with 6-[3H]thymidine. Estimates of the dose to cell nuclei in various tissues after the ingestion of [3H]thymidine were also made in order to predict more precisely possible radiation hazards.     

Out-of-field doses from secondary radiation produced in proton therapy and the associated risk of radiation-induced cancer from a brain tumor treatment

PurposeTo determine out-of-field doses produced in proton pencil beam scanning (PBS) therapy using Monte Carlo simulations and to estimate the associated risk of radiation-induced second cancer from a brain tumor treatment.MethodsSimulations of out-of-field absorbed doses were performed with MCNP6 and benchmarked against measurements with tissue-equivalent proportional counters (TEPC) for three irradiation setups: two irradiations of a water phantom using proton energies of 78–147 MeV and 177–223 MeV, and one brain tumor irradiation of a whole-body phantom. Out-of-field absorbed and equivalent doses to organs in a whole-body phantom following a brain tumor treatment were subsequently simulated and used to estimate the risk of radiation-induced cancer. Additionally, the contribution of absorbed dose originating from radiation produced in the nozzle was calculated from simulations.ResultsOut-of-field absorbed doses to the TEPC ranged from 0.4 to 135 µGy/Gy. The average deviation between simulations and measurements of the water phantom irradiations was about 17%. The absorbed dose contribution from radiation produced in the nozzle ranged between 0 and 70% of the total dose; the contribution was however small in absolute terms. The absorbed and equivalent doses to the organs ranged between 0.2 and 60 µGy/Gy and 0.5–151 µSv/Gy. The estimated lifetime risk of radiation-induced second cancer was approximately 0.01%.ConclusionsThe agreement of out-of-field absorbed doses between measurements and simulations was good given the sources of uncertainties. Calculations of out-of-field organ doses following a brain tumor treatment indicated that proton PBS therapy of brain tumors is associated with a low risk of radiation-induced cancer.     

Genetic efficacy of low doses of ionizing radiation in chronically-irradiated small mammals

Earlier we have established the genetic effects of low dose chronic irradiation in bank vole (somatic and germ cells, embryos), in pond carp (fertilized eggs, embryos, fry) and in laboratory mice (somatic and germ cells) in the range of doses from near-background to 10 cGy. These low dose effects observed in mammals and fish are not expected from extrapolation of high dose experiments. For understanding reasons this discrepancy the comparative analysis of genetic efficiency of low dose chronic irradiation and the higher doses of acute irradiation was carried out with natural populations of bank vole which inhabited the two sites differing in ground of radionuclide deposition. For comparing efficiency the linear regression model of dose-effect curve was used. Dose-effect equations were obtained for animals from two chronically irradiated bank vole populations. The mean population absorbed doses were in the range 0.04-0.68 cGy, the main part of absorbed doses consisted of external radiation of animals exposed to 137Cs gamma-rays. Dose-effect equations for acute irradiation to 137Cs gamma-rays (10-100 cGy) were determined for the same populations. Comparison of genetic efficiency was made by extrapolation, using regression coefficient beta and doubling dose estimation. For chronic exposure the doubling doses calculated from low-dose experiments are 0.1-2 cGy and the doubling doses determined from high-dose experiments are in the range of 5-20 cGy. Our hypothesis that the doubling dose estimate is calculated in higher-dose ionizing radiation experiments should be much higher than the deduced from the low dose line regression equation was verified. The doubling dose estimates for somatic cells of bank vole and those for germ cells of laboratory mice are in close agreement. The radiosensitivity of bank vole chromosomes were shown is practically the same as that for human lymphocytes since doubling dose estimates for acute irradiation close to each other. For low LET radiation a higher genetic efficiency of chronic low doses in comparison with the higher doses of acute gamma-irradiation (137Cs source) was proved by three methods.     

Investigation of gamma-irradiated vegetable seeds with high-resolution solid-state 13C NMR

13C solid-state NMR was used to investigate the effects of gamma radiation on vegetable seeds, Pisum sativum and Latuca sativa, at absorbed doses that inhibit their germination. By combining single-pulse excitation and cross-polarization experiments under magic angle spinning, both liquid and solid domains of seeds can be characterized. We showed that the liquid domains, mostly made of triacylglycerols (TAG), of vegetable seeds are not sensitive to radiation. The main structural changes have been observed in the embryonic axes of seeds when the seeds are water-imbibed before irradiation. These results rule out a starting hypothesis concerning the potential role of TAG contained in oil bodies as a potential source of aldehydes that could further react with DNA moiety.     

Effect of low doses of 14 MeV neutrons on polymers

The structural modifications of polymers irradiated with 14 MeV neutrons were studied. Two elastomers, a polypropylene-type polymer and poly(ethylene oxide) were exposed to low doses of fast neutrons in the range of 0.3-14 Gy. The radiation damages were observed at the molecular scale by infrared spectroscopy. The morphological changes were investigated by steric exclusion chromatography, insoluble fraction measurements, differential scanning calorimetry and X-ray diffraction. It was found that neutrons provoked oxidation processes accompanied by modifications in the polymer architecture, including chain scissions, crosslinking reactions and changes in the crystallinity. Moreover, the conventional antioxidants were shown to be inefficient in inhibiting the aging of the polymers. These results also suggest that the radiation damages could be used successfully for dosimetry applications using an easily implementable protocol.     

Cerebrovascular diseases in nuclear workers first employed at the Mayak PA in 1948–1972

Incidence and mortality from cerebrovascular diseases (CVD) (430–438 ICD-9 codes) have been studied in a cohort of 18,763 workers first employed at the Mayak Production Association (Mayak PA) in 1948–1972 and followed up to the end of 2005. Some of the workers were exposed to external gamma-rays only while others were exposed to a mixture of external gamma-rays and internal alpha-particle radiation due to incorporated ²³⁹Pu. After adjusting for non-radiation factors, there were significantly increasing trends in CVD incidence with total absorbed dose from external gamma-rays and total absorbed dose to liver from internal alpha radiation. The CVD incidence was statistically significantly higher among workers with total absorbed external gamma-ray doses greater than 0.20 Gy compared to those exposed to lower doses; the data were consistent with a linear trend in risk with external dose. The CVD incidence was statistically significantly higher among workers with total absorbed internal alpha-radiation doses to liver from incorporated ²³⁹Pu greater than 0.025 Gy compared to those exposed to lower doses. There was no statistically significant trend in CVD mortality risk with either external gamma-ray dose or internal alpha-radiation dose to liver. The risk estimates obtained are generally compatible with those from other large occupational studies, although the incidence data point to higher risk estimates compared to those from the Japanese A-bomb survivors. Further studies of the unique cohort of Mayak workers chronically exposed to external and internal radiation will allow improving the reliability and validating the radiation safety standards for occupational and public exposure.     

Morphologic study of tissue basophils of the skin in rats after acute local irradiation

A comparative morphological study was made of tissue basophils (TB) of rat skin at remote times (40, 70, 140, and 360 days) following single local exposure to soft and hard X-radiation with the doses at the skin surface of 15, 20, and 30 Gy. The TB response was maximum in the subepidermal and supramuscular layers of friable connective tissue. Changes in a median TB diameter were of a phase nature and a function of radiation dose absorbed in the skin layers under study.     

Effects of N-trifluoroacetyladriamycin-14-O-hemiadipate and radiation on L1210 cells

N-Trifluoroacetyladriamycin-14-O-hemiadipate (AD 143) is the most active among the 14-O-hemiester adriamycin-trifluoroacetamide derivatives and has been selected for preclinical studies. We now report its ability to enhance the kill by ionizing radiation of murine leukemic cells in culture. A 1-h exposure to either 1.28-12.8 micrograms/ml of AD 143 or to 0.16-1.62 micrograms/ml of adriamycin (ADR) was followed at 0 h by graded doses (0-1 Krad) of radiation, and cell viability was assessed by soft agar cloning technique. Regression analyses of the dose-response curve have shown that both compounds, at the concentrations employed, decrease the reciprocal of the slope D0 from 97 rad for radiation alone, to 66-56 rad for AD 143 (1.28-5.12 micrograms/ml) plus radiation, or to 85-61 rad for ADR (0.16-0.65 micrograms/ml) when used with radiation. ADR, however, had a significant "shoulder"-modifying effect. The Dq remained essentially unchanged after AD 143 pretreatment. Quantitation of synergism (superadditivity), additivity, and antagonism was performed by isobologram analysis and by a computerized method based on the "median effect principle." Both approaches have shown that synergism of AD 143 or ADR with radiation becomes apparent with dose escalation. This effect is discernible at significantly lower levels of AD 143 than of ADR, corresponding to less than LD50 measured by the clonogenic assay.     

Intestinal absorption and tissue distribution of [14C]pyrroloquinoline quinone in mice.

Pyrroloquinoline quinone (PQQ) functions as a cofactor for prokaryotic oxidoreductases, such as methanol dehydrogenase and membrane-bound glucose dehydrogenase. In animals fed chemically defined diets, PQQ improves reproductive outcome and neonatal growth. Consequently, the present study was undertaken to determine the extent to which PQQ is absorbed by the intestine, its tissue distribution, and route of excretion. About 28 micrograms of PQQ (0.42 microCi/mumol), labeled with 14C derived from L-tyrosine, was administered orally to Swiss-Webster mice (18-20 g) to estimate absorption. PQQ was readily absorbed (62%, range 19-89%) in the lower intestine, and was excreted by the kidneys (81% of the absorbed dose) within 24 hr. The only tissues that retained significant amounts of [14C]PQQ at 24 hr were skin and kidney. For kidney, it was assumed that retention of [14C]PQQ represented primarily PQQ destined for excretion. For skin, the concentration of [14C]PQQ increased from 0.3% of the absorbed dose at 6 hr to 1.3% at 24 hr. Furthermore, most of the [14C]PQQ in blood (greater than 95%) was associated with the blood cell fraction, rather than plasma.     

Variation in the frequencies of spontaneous and in vitro induced chromosome aberrations in human lymphocytes during natural and radiation-induced aging

The frequency of translocations detected by FISH in lymphocytes of control donors increases with age as a quadratic function. This process is faster in persons previously exposed to low doses of radiation. It means that translocation frequency can be used as a measure of biological age. Moreover, translocation frequency should be taken into account in biological reconstruction of absorbed doses. The frequencies of dicentrics detected by FIGH and FPG linearly increase with age in both groups, and this process occurs at equal rates during natural and radiation-induced aging. The age-dependent increase in the frequency of translocations exceeds the increase in dicentrics. The radiation sensitivity of lymphocytes estimated from the frequency of in vitro induced chromosomal aberrations tends to increase with age in the control group and decreases significantly in the group exposed to radiation; i.e., low-dose preexposure alters the pattern of the age dependence of radiation sensitivity in lymphocytes in vitro.     

Cobalt-60 gamma radiation increased the nitric oxide generation in cultured rat vascular smooth muscle cells

Radiation is a promising and new treatment for restenosis following angioplasty. Nitric oxide has been proposed as a potential "anti-restenotic" molecule. We radiated the cultured rat vascular smooth muscle cells with Cobalt-60 gamma radiation at doses of 14 and 25Gy and observed nitrite production, cGMP content, L-arginine uptake, inducible nitric oxide synthase (iNOS) activity, and the gene expression of iNOS. Results showed that radiation at doses of 14 and 25Gy increased cGMP content by 92.4% and 86.4%, respectively. Radiation at the dose of 25Gy increased the iNOS activity and nitrite content, but radiation at the dose of 14Gy had no significant effect on iNOS activity and NO production. Both doses of radiation significantly decreased the L-arginine transport. Radiation at the doses of 14 and 25Gy increased iNOS gene expression significantly, which was consistent with the effect of radiation on iNOS activity. In conclusion, radiation induces the NO generation by up-regulating the iNOS activity.     

Factors affecting total dissolved solids concentration of γ-ray-irradiated aqueous hexamethylenetetramine solution: A dosimetric study

A new γ-ray-radiation dosimetric system (TDS-HMTA), comprising a 'total dissolved solids (TDS)' meter and 0.02 M aqueous hexamethylenetetramine (HMTA) solution, is introduced for medical and biological applications. Gamma-ray radiolysis of aqueous HTMA solutions increases the concentrations (ppm) of TDS, which is measured by the TDS meter. The effects of HMTA concentration, absorbed radiation dose, absorbed dose rate, and storage time on the TDS concentration of irradiated HMTA solutions were studied. It was found that 0.02 M aqueous HMTA solution yields the highest sensitivity to γ-ray-radiation according to TDS concentration measurements. The effect of absorbed radiation dose was studied in the range 1.64–435.5 kGy. The TDS concentration increases linearly up to the maximum of the studied absorbed radiation dose range (R² = 0.9965). The overall coefficient of variation (CV %) associated with TDS concentration measurements of 0.02 M HMTA solution as a function of absorbed dose was found to be 0.732%. The effect of dose rate on the TDS concentration was studied in the range 0.33–3.31 kGy/h. It was found, also, that the TDS concentration is relatively stable over a storage period of 144 h after irradiation with different doses. The tissue equivalency of 0.02 M aqueous HMTA solutions allow it to be used for radiation dose measurement during sterilization in human tissue banks. Therefore, this system (TDS–HMTA) could be considered as a promising candidate for γ-ray radiation dosimetry in technical, medical and research fields.     

14C UPTAKE BY THE MARINE ANGIOSPERM PHYLLOSPADIX SCOULERP

Rhizomes and attached leaves of Phyllospadix scouleri Hook, were collected in the intertidal zone along the central California coast and exposed to a solution of NaH¹⁴CO₃ in seawater under controlled laboratory conditions. Over a 90-min period roots and rhizomes absorbed very little ¹⁴C compared to leaves. Translocation during that time was minor. Plants pretreated with the photosynthetic inhibitor DCMU showed no ¹⁴C uptake, indicating that under normal circumstances the carbon which is absorbed by leaves is fixed and accumulates as photosynthate. The rate of gross photosynthesis was about 13 mg CO₂ g dry wt⁻¹ hr⁻¹. Gross photosynthesis of wet leaves exposed to ¹⁴CO₂ in air was significantly less than leaves exposed to NaH¹⁴CO₃. The effect of a leaf-grazing limpet (Notoacmea paleacea) on leaf anatomy and ¹⁴C uptake is discussed.     

Modeling radiation dose and effects from internal emitters in nuclear medicine: from the whole body to individual cells.

In nuclear medicine, proper application of radiation protection principles depends on balancing the potential risks of exposure to ionizing radiation against its possible benefits. Average doses to organs, in diagnostic or therapeutic applications, are not always representative of the doses received at the tissue or cellular level. Therefore, understanding of the relationship between the overall biological effect and absorbed dose delivered by the radiopharmaceutical may require study of doses at the organ, tissue, or cell level. In this paper, we review current models for radiation dose assessment, with consideration of the different models and assumptions employed for study at all levels of investigation.