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Comparative radiation tolerance based on the induction of DNA double-strand breaks in tobacco BY-2 cells and CHO-K1 cells irradiated with gamma rays.

Higher plants are generally more tolerant to ionizing radiation than mammals. To explore the radiation tolerance of higher plants, the induction of DNA double-strand breaks (DSBs) by gamma rays was investigated in tobacco BY-2 cells and compared with that in Chinese hamster ovary (CHO)-K1 cells as a reference. This is the first examination of radiation-induced DSBs in a higher plant cell. The resulting DNA fragments were separated by pulsed-field gel electrophoresis and stained with SYBR Green I. The initial yield of DSBs was then quantified from the fraction of DNA fragments shorter than 1.6 Mbp based on the assumption of random distribution of DSBs. The DSB yield in tobacco BY-2 cells (2.0 +/- 0.1 DSBs Gbp(-1) Gy(-1)) was only one-third of that in CHO-K1 cells. Furthermore, the calculated number of DSBs per diploid cell irradiated with gamma rays at the mean lethal dose was five times greater in BY-2 cells (263 +/- 13) than in CHO-K1 cells. These results suggest that the radiation tolerance of BY-2 cells appears to be due not only to a lower induction of DNA damage but also to a more efficient repair of the induced DNA damage.

Animals↗

Sequence diversity of rulA among natural isolates of Pseudomonas syringae and effect on function of rulAB-mediated UV radiation tolerance.

The rulAB locus confers tolerance to UV radiation and is borne on plasmids of the pPT23A family in Pseudomonas syringae. We sequenced 14 rulA alleles from P. syringae strains representing seven pathovars and found sequence differences of 1 to 12% within pathovar syringae, and up to 15% differences between pathovars. Since the sequence variation within rulA was similar to that of P. syringae chromosomal alleles, we hypothesized that rulAB has evolved over a long time period in P. syringae. A phylogenetic analysis of the deduced amino acid sequences of rulA resulted in seven clusters. Strains from the same plant host grouped together in three cases; however, strains from different pathovars grouped together in two cases. In particular, the rulA alleles from P. syringae pv. lachrymans and P. syringae pv. pisi were grouped but were clearly distinct from the other sequenced alleles, suggesting the possibility of a recent interpathovar transfer. We constructed chimeric rulAB expression clones and found that the observed sequence differences resulted in significant differences in UV (wavelength) radiation sensitivity. Our results suggest that specific amino acid changes in RulA could alter UV radiation tolerance and the competitiveness of the P. syringae host in the phyllosphere.

Alleles↗

Long-term consequences of chemotherapeutic agents on hematopoiesis: development of altered radiation tolerance.

The long-term effects of chemotherapeutic agents on subsequent radiation tolerance of the hematopoietic marrow were studied after a single injection of doxorubicin, 5-fluorouracil, or cyclophosphamide at a maximum tolerated dose. At designated intervals following drug treatment, drug-treated and age-matched control male B6D2F1 mice were exposed to 4.5 Gy of total-body irradiation, and the recovery kinetics of the stem cell (assayed at days 8 and 13 colony-forming spleen units) and progenitor (burst-forming erythroid units, and colony-forming erythroid and granulocyte/macrophage units) compartments were established. Response deficits were calculated for each compartment by comparison of treated and control recovery curves at 5 intervals over 32 weeks. Based on these response deficits, a number of conclusions were drawn: 1) There is selective drug specificity for the more primitive (13d) and mature (8d) CFUs subpopulations; 2) these sensitivities determine the temporal consequences of drug treatment on subsequent radiation tolerance in the marrow (e.g., acute, delayed, or long term); and 3) drugs that influence long-term radiation tolerance of the marrow are dose dependent and initially affect the more primitive stem cells. The data suggest that the initial lesion in the stem cell compartment, resulting in long-term enhancement of radiosensitivity, involves a major restriction (either in cell number or in genetic functionality) of the proliferative potential necessary for recovery from subsequent radiation insult.

Animals↗

Radiation tolerance in the eutardigrade Richtersius coronifer.

PURPOSE: Tardigrades have a reputation of being extremely tolerant to extreme environmental conditions including tolerance to ionizing radiation while in a desiccated, anhydrobiotic state. However, the evidence for radio-tolerance in tardigrades is based on only one previous report, and there is an obvious need for complementary studies. In this paper we report an investigation on radio-tolerance in desiccated and hydrated specimens of the eutardigrade Richtersius coronifer. MATERIALS AND METHODS: Groups of 30 - 50 tardigrades were exposed to gamma-radiation at doses between 1.0 - 9.0 (anhydrobiotic animals) or 0.5 - 5.0 (hydrated animals) kGy and the animals were followed until all were dead. Radiation tolerance of both desiccated and hydrated tardigrades was studied. RESULTS: Both desiccated and hydrated animals irradiated with 0.5 and 1 kGy did not deviate in survival from the control groups. Animals from all exposed groups underwent their moulting and egg production cycle, but at decreasing frequency for doses above 1 kGy. No eggs laid by irradiated animals hatched, while eggs laid by controls did so. CONCLUSION: Our study suggests that radiation tolerance in tardigrades is not due to biochemical protectants connected with the desiccated state. Rather, cryptobiotic tardigrades may rely on efficient mechanisms of DNA repair, the nature of which is currently unknown.

Animals↗

Correlation of radiation tolerance dose of normal human organs with organ weight, blood, and water content.

The concerted effort to minimize the radiation exposure to normal human tissues while delivering a high radiation dose to the tumor often results in complications. This limits the efficacy of radiation treatment. Analysis of radiation tolerance dose with organ weight in 15 human organs yields a correlation coefficient of 0.62, whereas the correlation of radiation tolerance dose with blood and water content yields correlation coefficients of 0.82 and 0.60, respectively. Results indicate that as the organ weight and/or blood and water content increases, radiation tolerance dose decreases.

Blood↗

Radiation tolerance of complex oxides

The radiation performance of a variety of complex oxides is predicted on the basis of a material's propensity to accommodate lattice point defects. The calculations indicate that a particular class of oxides possessing the fluorite crystal structure should accept radiation-induced defects into their lattices far more readily than a structurally similar class of oxides based on the pyrochlore crystal structure. Preliminary radiation damage experiments substantiate the prediction that fluorites are inherently more radiation resistant than pyrochlores. These results may permit the chemical durability and radiation tolerance of potential hosts for actinides and radioactive wastes to be tailored.

Journal Article↗

Radiation tolerance of the liver in relation to the preserved functional capacity.

The radiation tolerance of the liver was investigated in 12 patients, 11 of them with liver cirrhosis, treated for hepatocellular carcinoma by partial liver irradiation with doses between 50 and 77 Gy. The tolerance was assessed by the complication probability (Lyman's model), which concerned the injured tissue itself, and by a prediction score used for postsurgical liver failure, which concerned the preserved functional capacity, assuming that the > or = 30 Gy volume was equivalent to the resected volume. The prediction score corresponded better with the observed risk of fatal liver failure than the complication probability. The liver volume after radiotherapy correlated largely with the untreated volume and the low-dose volume. Thus the preserved functional capacity gives a better expression of the radiation tolerance than direct measures of the extent of injured tissue.

Aged↗

Radiation-induced liver disease in three-dimensional conformal radiation therapy for primary liver carcinoma: the risk factors and hepatic radiation tolerance.

PURPOSE: To identify risk factors relevant to radiation-induced liver disease (RILD) and to determine the hepatic tolerance to radiation. METHODS AND MATERIALS: The data of 109 primary liver carcinomas (PLC) treated with hypofractionated three-dimensional conformal radiation therapy (3D-CRT) were analyzed. Seventeen patients were diagnosed with RILD and 13 of 17 died of it. RESULTS: The risk factors for RILD were late T stage, large gross tumor volume, presence of portal vein thrombosis, association with Child-Pugh Grade B cirrhosis, and acute hepatic toxicity. Multivariate analyses demonstrated that the severity of hepatic cirrhosis was a unique independent predictor. For Child-Pugh Grade A patients, the hepatic radiation tolerance was as follows: (1) Mean dose to normal liver (MDTNL) of 23 Gy was tolerable. (2) For cumulative dose-volume histogram, the tolerable volume percentages would be less than: V5 of 86%, V10 of 68%, V15 of 59%, V20 of 49%, V25 of 35%, V30 of 28%, V35 of 25%, and V40 of 20%. (3) Tolerable MDTNL could be estimated by MDTNL (Gy) = -1.686 + 0.023 * normal liver volume (cm3). CONCLUSION: The predominant risk factor for RILD was the severity of hepatic cirrhosis. The hepatic tolerance to radiation could be estimated by dosimetric parameters.

Adult↗

[Radiation tolerance of normal lung-pulmonary radiation syndrome].

Radiation pneumonitis and radiation fibrosis are two distinct syndromes with probably different target cells. The ultrastructural changes occur rapidly and current evidence suggests that damage to the type II pneumocyte and the endothelial cell is linked to the pneumonia process than the fibrotic. The fibrosis process may be related to the basement membrane of both endothelial cells and alveolar type I cells. Dose time and volume data for tolerance dose are well documented in animals. Many antineoplastic agents enhances radiation lung damage. The pneumonitis and fibrosis will be discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Radiation tolerance of cirrhotic livers in relation to the preserved functional capacity: analysis of patients with hepatocellular carcinoma treated by focused proton beam radiotherapy.

PURPOSE: To determine the preserved functional capacity of the liver as a probable determinant of radiation tolerance in patients with cirrhosis and hepatocellular carcinoma, who underwent proton beam radiotherapy. MATERIALS AND METHODS: We reviewed computed tomographic (CT) scans of 26 patients with cirrhosis and hepatocellular carcinoma during a period of 12-27 months after proton beam radiotherapy. Tumors were treated with focused proton beams with target doses of 140-186 TDF (time, dose, and fractionation). We measured the degree of hypertrophy of the untreated liver volume by measuring the total liver volume and the treated liver volume which was radiologically identified on contrast-enhanced CT scans. The risk of radiation-induced liver failure was estimated using the prediction score (PS) originally used for estimating posthepatectomy liver failure, substituting the planned treated liver volume for the resection liver volume. RESULTS: The degree of hypertrophy ranged from -19% to 51%, and was significantly positively correlated with the ratio of the planned treated liver volume to the functional liver volume. The PS agreed well with observed radiation tolerance in 21 patients, but underestimated the tolerance in 5. This underestimation was diminished when the PS was recalculated using the identified untreated liver volume in lieu of the planned untreated liver volume. CONCLUSION: As in surgical treatment, radiation tolerance of the cirrhotic liver after focused treatment is closely related to the preserved functional capacity of the identified untreated liver volume, which shows compensatory hypertrophy following radiotherapy.

Aged↗

Biological effects of anhydrobiosis in an African chironomid, Polypedilum vanderplanki on radiation tolerance.

PURPOSE: Anhydrobiotic organisms are known to have an extremely high tolerance against a range of stresses. However, the functional role of anhydrobiosis in radiation tolerance is poorly understood, especially in development following irradiation. The present study aims to evaluate effects of anhydrobiosis on radiation tolerance in an anhydrobiotic insect, Polypedilum vanderplanki. MATERIALS AND METHODS: Larval survival (48 h), anhydrobiotic ability, metamorphosis and reproduction after exposure to 1-9000 Gy of gamma-rays at the larval stage were compared between anhydrobiotic (dry) and normal (wet) phases. RESULTS: Wet larvae were killed in a dose-dependent manner at doses higher than 2000 Gy, and all died within 8 h after 4000 Gy exposure. In contrast, dry larvae survived even 5000 Gy, and some of them still tolerated 7000 Gy and were alive at 48 h after rehydration. Moreover, greater radiotolerance of dry larva, compared to wet ones, was demonstrated in terms of metamorphoses. However, anhydrobiosis did not protect against radiation damage in terms of producing viable offspring. CONCLUSION: These results indicate that anhydrobiosis enhances radiotolerance, resulting in increases of successful metamorphoses.

Animals↗

Gianturco expandable wire stents in the treatment of superior vena cava syndrome recurring after maximum-tolerance radiation.

Two patients with superior vena cava syndrome (SVCS) recurring after maximum-tolerance radiation were treated by placing a Gianturco expandable wire stent (GEWS) into the obstructed superior vena cava. The SVCS symptoms rapidly disappeared and good short-term (6 months) palliation was achieved. GEWS placement is a promising therapeutic alternative for palliation of SVCS symptoms when other therapeutic modes cannot be used or are not effective.

Carcinoma, Squamous Cell↗

Effect of cycloheximide on skin and renal radiation tolerance in the rat.

The effect of cycloheximide (CHM) on skin and renal radiation tolerance in the rat has been studied. When administered 24 hr prior to a range of single radiation doses to the hind limbs, the drug protected against skin damage. When administered at intervals of 45 min to 100 hr prior to single-dose irradiation of the kidneys, no protection against renal injury, as manifested by blood pressure, urine creatinine level, and lethality, was observed. CHM-induced alteration in the cell cycle may confer radioprotection to a rapidly proliferating cell renewal system such as the skin and exert no radioprotective action in slowly proliferative tissue such as kidney.

Animals↗

Estimation of radiation tolerance to high LET heavy ions in an anhydrobiotic insect, Polypedilum vanderplanki.

PURPOSE: Anhydrobiotic larvae of Polypedilum vanderplanki are known to show an extremely high tolerance against a range of stresses. We have recently reported that this insect withstands exposure to high doses of gamma-rays (linear energy transfer [LET] 0.2 keV/microm). However, its tolerance against high LET radiation remains unknown. The aim of this study is to characterize the tolerance to high-LET radiations of P. vanderplanki. MATERIALS AND METHODS: Larval survival and subsequent metamorphoses were compared between anhydrobiotic (dry) and non-anhydrobiotic (wet) samples after exposure to 1 - 7000 Gy of three types of heavy ions delivered from the azimuthally varying field (AVF) cyclotron with LET values ranging from 16.2 - 321 keV/microm. The tolerance against 4He ions was also compared among three chironomid species. RESULTS: At all LET values measured, dry larvae consistently showed greater radiation tolerance than hydrated larvae, perhaps due to the presence of high concentrations of the disaccharide trehalose in anhydrobiotic animals, and the radiation-induced damage became evident at lower doses as development progressed. Relative biological effectiveness (RBE) values based on the median inhibitory doses reached a maximum at 116 keV/microm (12C), and the maximum RBE clearly increased as development progressed. Lower D0 (dose to reduce survival from relative value 1.00 - 0.37 on the exponential part of the survival curve), and higher Dq (quasi-threshold dose) were found in individuals exposed to 4He ions, compared to gamma-rays, and in P. vanderplanki larvae compared to non-anhydrobiotic chironomids. CONCLUSION: Anhydrobiosis potentiates radiation tolerance in terms of larval survival, pupation and adult emergence of P. vanderplanki exposed to high-LET radiations as well as to low-LET radiation. P. vanderplanki larvae might have more efficient DNA damage repair after radiation than other chironomid species.

Animals↗

[Radiation tolerance of partially irradiated liver in a multidisciplinary treatment for hepatoma].

Radiation tolerance of the partially irradiated liver was studied in eight patients with primary hepatoma treated by a multimodal approach. Seven patients were treated by transarterial embolization therapy (TAE) with Lipiodol-MMC, and two patients were treated by operation, combined with radiotherapy. Six patients had liver cirrhosis and the other one had renal dysfunction. Respiration-gated irradiation was employed to reduce a treatment volume for seven patients. Radiation portals were carefully tailored using the embolized Lipiodol or a metal clip inserted into the tumor as references. Two or three portals were used for each patient. The treatment volume ranged from 64 to 1400 cm3. The target dose ranged from 50.4 Gy to 81.0 Gy, from 73.5 to 108.6 in TDF. Liver function tests (GOT, GPT, LDH, ALP, ChE and total Bilirubin) were examined for 30 weeks after initiation of irradiation. Three patients showed abnormal value in more than 5 tests. Of these three patients, the hepatic hilum was included in the treatment volume in two, and the tumor progressed during the observation period in two. Leukopenia and thrombopenia were observed, but these values were not below 2000 and 40000/mm3, respectively, although the thrombocyte count before irradiation was below 100000/mm3 in 7 patients. AFP titers decreased after the treatment in six out of seven patients with abnormally elevated pretreatment titer. The survival period after staring irradiation was 6.5 to 25 months. "The volume dose" did not correlate well with the degree of the liver function aggravation.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular↗

Deinococcus deserti sp. nov., a gamma-radiation-tolerant bacterium isolated from the Sahara Desert.

Two gamma- and UV-radiation-tolerant, Gram-negative, rod-shaped bacterial strains, VCD115T and VCD117, were isolated from a mixture of sand samples collected in the Sahara Desert in Morocco and Tunisia, after exposure of the sand to 15 kGy gamma radiation. Phylogenetic analysis based on 16S rRNA gene sequences and DNA-DNA hybridizations showed that VCD115T and VCD117 are members of a novel species belonging to the genus Deinococcus, with Deinococcus grandis as its closest relative. The DNA G+C contents of VCD115T and VCD117 are 59.8 and 60.6 mol%, respectively. The major fatty acids (straight-chain 15 : 1, 16 : 1, 17 : 1 and 16 : 0), polar lipids (dominated by phosphoglycolipids and glycolipids) and quinone type (MK-8) support the affiliation to the genus Deinococcus. The strains did not grow on rich medium such as trypticase soy broth (TSB), but did grow as whitish colonies on tenfold-diluted TSB. The genotypic and phenotypic properties allowed differentiation of VCD115T and VCD117 from recognized Deinococcus species. Strains VCD115T and VCD117 are therefore identified as representing a novel species, for which the name Deinococcus deserti sp. nov. is proposed, with the type strain VCD115T (=DSM 17065T=LMG 22923T).

Africa, Northern↗

Increased radiation tolerance of mouse tongue epithelium after local conditioning.

The effect of local stimulation on mitotic activity and radiation tolerance was studied in mouse tongue mucosa. Silver nitrate solution (0.5-20%) was used for local conditioning. The most effective protocol comprised three daily treatments (days 0-2), yielding a delayed increase in 24 h mitotic counts by about 30% on days 5-7. The stimulating effect was independent of silver nitrate concentration. Sham treatment with saline or anaesthesia alone clearly depressed mitotic activity on days 2-4 without any subsequent overshoot. Radiation treatment was initiated on day 5 after three daily treatments with 3% silver nitrate solution. A top-up technique was employed, consisting of fractionated irradiation (300 kV X-rays) of the whole snout, followed by graded local test doses (25 kV X-rays) to induce denudation in a confined area of the inferior tongue surface. Silver nitrate conditioning did not alter the radiosensitivity of the epithelium to single local doses, but shortened the latency to denudation from 11 to 8 days. In contrast, a clear increase in tolerance to fractionated irradiation, delivering 5 x 2.5, 5 x 3.5, 5 x 4.5 Gy or 3 x 5.2 Gy in 7 days, was observed, equivalent to about four, two, one and two extra dose fractions. This approach may be a suitable way to increase radiation tolerance of oral mucosa in clinical radiotherapy.

Animals↗

Can dose-response models predict reliable normal tissue complication probabilities in radical radiotherapy of urinary bladder cancer? The impact of alternative radiation tolerance models and parameters.

PURPOSE: To analyze the consequences of selecting alternative normal tissue complication probability (NTCP) models and parameters for evaluation of radiotherapy of urinary bladder cancer. METHODS AND MATERIALS: Treatment plans of 24 bladder cancer patients referred to radical 4-field conformal radiotherapy were analyzed. Small intestinal and rectal NTCPs were determined using both the probit and relative seriality models with several sets of published radiation tolerance parameters. Various combinations of NTCP models and parameters were applied to find the prescription dose in individual patients as well as to estimate the benefit of the conformal radiotherapy setup. RESULTS: Different risk estimates were predicted from the two NTCP models, even when the same clinical radiation tolerance doses were fitted into the two models. The demonstrated variability translated into significant deviations (7-10 Gy) in the recommended prescription doses. Even if it was possible to discriminate between a 2-field plan and the 4-field conformal setup using a given complication model and set of tolerance parameters, the estimated benefit of the conformal treatment in terms of permitted dose escalation varied with as much as 10-12 Gy between the different NTCP models/parameters used. CONCLUSION: Different NTCP models and tolerance parameters might propose different answers to important clinical questions in radiotherapy treatment of bladder cancer, such as dose prescription and scoring of rival treatment plans. We therefore recommend that the variability caused by tolerance parameter uncertainty and model selection should be taken into account in dose-response modeling of radiotherapy treatment.

Aged↗