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Results for “Radiation Tolerance”

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PubMed1985

Effect of prolonged expansion of marrow progenitor compartments following doxorubicin (ADR) on subsequent radiation tolerance.

The long-term effects of a maximum tolerated dose of doxorubicin (ADR) (10 mg/kg, LD10/60) on the recovery of the hematopoietic compartments of the femoral marrow from radiation (450 rad) were investigated over a 32-week interval using a mouse model. Comparative radiation response curves, estimating hematopoietic proliferative potential, were used to establish response deficits (RD) for individual compartments of ADR-treated marrow. The RD data suggest that two potentially discrete lesions result from ADR treatment: one lesion associated with acute toxicity and a second developing 8-16 weeks after drug treatment. A depletion of the older hematopoietic stem cell (CFU-S8d) compartment was observed to accompany the development of the second lesion. Data are presented suggesting that both initial stem cell kill, as well as an accelerated aging of the CFU-S8d by prolonged expansion of progenitors, eventually lead to a depletion of stem cell reserve manifested by a progressive loss of radiotolerance with time.

Animals↗
PubMed2003

Radiation tolerance of the rat spinal cord after single and split doses of photons and carbon ions.

The sensitivity of the rat spinal cord to single and split doses of radiation and the resulting relative biological effectiveness (RBE) were determined for carbon-ion irradiations (12C) in the plateau and Bragg-peak regions. The cranial part of the cervical and thoracic spinal cords of 180 rats were irradiated with one or two fractions of 12C ions or photons, respectively. Dose-response curves for the end point symptomatic myelopathy were established, and the resulting values for the ED50 (dose for 50% complication probability) were used to determine the RBEs. A median latency for myelopathy of 167 days (range, 121-288 days) was found. The ED50 values were 17.1 +/- 0.8 Gy, 24.9 +/- 0.7 Gy (one and two fractions, 12C plateau) and 13.9 +/- 0.8, 15.8 +/- 0.7 Gy (one and two fractions, 12C Bragg peak), respectively. For photons we obtained ED50 values of 24.5 +/- 0.8 Gy for single doses and 34.2 +/- 0.7 Gy when two fractions were applied. The corresponding RBEs were 1.43 +/- 0.08, 1.37 +/- 0.12 (one and two fractions, 12C plateau) and 1.76 +/- 0.05, 2.16 +/- 0.11 (one and two fractions, 12C Bragg peak), respectively. Hematoxylin and eosin staining revealed necrosis of the white matter in the spinal cord in all symptomatic animals. In summary, from one- and two-fraction photon, 12C plateau and Bragg-peak irradiation of the rat spinal cord, we have established RBEs as well as the individual ED50's. From the latter there is a clear indication of repair processes for fractionated photons and 12C plateau ions which are significantly reduced by using Bragg-peak ions. Additional studies are being carried with 6 and 18 fractions to further refine and define the RBE and ED50 values and estimate the alpha/beta ratios.

Adaptation, Physiological↗
PubMed2006

Radiation tolerance in the tardigrade Milnesium tardigradum.

PURPOSE: Tardigrades are known to survive high doses of ionizing radiation. However, there have been no reports about radiation effects in tardigrades under culture conditions. In this study, we investigated tolerance of the tardigrade, Milnesium tardigradum, against gamma-rays and heavy ions by determining short-term or long-term survival, and reproductive ability after irradiation. MATERIALS AND METHODS: Hydrated and anhydrobiotic animals were exposed to gamma-rays (1000 - 7000 Gy) or heavy ions (1000 - 8000 Gy) to evaluate short-term survival at 2, 24 and 48 h post-irradiation. Long-term survival and reproduction were observed up to 31 days after irradiation with gamma-rays (1000 - 4000 Gy). RESULTS: At 48 h after irradiation, median lethal doses were 5000 Gy (gamma-rays) and 6200 Gy (heavy ions) in hydrated animals, and 4400 Gy (gamma-rays) and 5200 Gy (heavy ions) in anhydrobiotic ones. Gamma-irradiation shortened average life span in a dose-dependent manner both in hydrated and anhydrobiotic groups. No irradiated animals laid eggs with one exception in which a hydrated animal irradiated with 2000 Gy of gamma-rays laid 3 eggs, and those eggs failed to hatch, whereas eggs produced by non-irradiated animals hatched successfully. CONCLUSION: M. tardigradum survives high doses of ionizing radiation in both hydrated and anhydrobiotic states, but irradiation with >1000 Gy makes them sterile.

Animals↗
PubMed2004

Modulation of rodent spinal cord radiation tolerance by administration of platelet-derived growth factor.

PURPOSE: To examine the role of platelet-derived growth factor (PDGF) for ameliorating radiation myelopathy of the cervical spinal cord in a rodent model. METHODS AND MATERIALS: After developing the technique for cannulation of the basal cistern, initial animal experiments were conducted to test the feasibility of intrathecal continuous infusion of PDGF in a model of cervical spinal cord irradiation in adult Fisher F-344 rats and to determine the most effective dose level of PDGF. Subsequently, the dose-modification factor was determined in a larger group of rats. Irradiation was given in 2 fractions (16 Gy followed by 14-24 Gy) and animals were examined for the development of paresis. RESULTS: The initial dose-finding experiment revealed significant differences in the incidence of radiation myelopathy (100% in saline-treated control rats, 25% with the most effective dose of PDGF, up to 100% with less effective doses). The most effective dose of PDGF was 0.014 mug per day. Subsequent experiments revealed a median effective dose (ED(50)) of 35.6 Gy (95% confidence interval, 34.7-36.5 Gy) for animals receiving this dose of PDGF in contrast to 33.8 Gy (33.4-34.3 Gy) for the control group (p = 0.003). The dose-modification factor obtained with this dose of PDGF was 1.05. CONCLUSIONS: Intrathecal administration of PDGF concomitant to irradiation of the cervical spinal cord in rats was feasible. Treatment with PDGF significantly increased the tolerance of the spinal cord. The PDGF experiments should be viewed as a proof of principle that brief therapeutic intervention in the earliest phase of damage induction can reduce late effects in the spinal cord. They form the basis for further studies of growth factor administration in this particular model.

Animals↗
PubMed1986

The effect of low dose-rate and cyclophosphamide on the radiation tolerance of the mouse lung.

Mice were given cyclophosphamide 30 mg/kg intraperitoneally before thoracic irradiation at high dose-rate (HDR, 100 cGy/min) or low dose-rate (LDR, 5 cGy/min). The development of pneumonitis was monitored by regular measurement of breathing rate. Peak rises in breathing rate occurred around 4-9 weeks in those given cyclophosphamide before irradiation, and around 14-16 weeks in those given radiation alone, regardless of dose-rate. The dose reduction factor (DRF = LDR/HDR ratio) for LDR irradiation was congruent to 1.8 but LDR sparing was abolished (DRF congruent to 1.0) when cyclophosphamide was given before irradiation.

Animals↗
PubMed1987

[Analysis of tolerable radiation dose on the oral mucosa and mandibular bone--external beam and/or brachytherapy].

Cooperative study from six institutes was made for the late radiation damage of oral mucosa and mandibular bone. Analysis was made for the selected patients with oropharyngeal cancer for external beam alone and with tongue cancer for interstitial implant. All of them were followed at least two years without recurrence having no secondary treatment after initial radiotherapy. As for external beam alone, frequency of the mucosal ulcer was not increased with high dose level, but tolerance dose for the oral mucosa was limited from associated mandibular damage. Late damages were not likely after brachytherapy alone.

Brachytherapy↗
PubMed1999

[Natural plasmid pSD89 (Cmr) from Salmonella derby K89, which increases the radiation tolerance of Escherichia coli strain K-12].

Several plasmids with molecular mass of 1.3-9 MDa were found in a clinical isolate of Salmonella derby K89 by electrophoresis in agarose gel. One of these plasmids, designated pSD89 (Cmr), was derived from the K89 strain via transformation of the plasmidless recipient S. derby K82 to chloramphenicol resistance. The plasmid-carrying strain K89 and the K82 strain completely cured of plasmids were equally sensitive to the lethal action of UV light, whereas the plasmid-carrying strain was even more sensitive to ionizing radiation than the plasmidless variant. Nevertheless, transformants carrying only plasmid pSD89 (Cmr) were found to be more resistant to gamma-rays and UV light than the recipient. By using an intermediate host Escherichia coli Z80 (r-m+), plasmid pSD89 (Cmr) was introduced into different E. coli K-12 strains: polA-, recA-, uvrA-, umuC-, and the wild-type strain. A slight increase in radioresistance of E. coli wild-type cells and a significant complementation of a repair defect in recA and polA mutants, but not in uvrA and umuC, were observed.

Chloramphenicol Resistance↗