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PubMed1995

Effects of topoisomerase I-targeted drugs on radiation response of L5178Y sublines differentially radiation and drug sensitive.

The murine L5178Y (LY) lymphoma sublines, LY-R (radiation resistant) and LY-S (radiation sensitive) display a difference in susceptibility to camptothecin (CPT): LY-S cells are less sensitive to killing by this inhibitor of topoisomerase I than LY-R cells. Post-treatment (CPT present until 3 h after irradiation) sensitizes only LY-S cells. In agreement with this, only in LY-S cells is the relative number of DNA-protein cross-links formed after treatment with CPT + X higher than expected for additivity of X-ray and CPT-induced damage. The pattern of changes in the labelling indices and cell cycle distribution in cells that underwent combined treatment is essentially like that seen for single-agent treatment: for LY-S cells like that for radiation, for LY-R cells like that for CPT. We found no direct relation between the patterns of cell cycle distributions and the enhancement of the lethal effect of X-irradiation by CPT post-treatment. The sublines are not markedly differentially sensitive to beta-lapachone, which modifies topoisomerase I activity, and not sensitized to X-rays by post-irradiation treatment with the drug.

Animals↗

PubMed2001

Response of radiation protection dosemeters in mixed high-energy photon and electron radiation fields.

The response of radiation protection dosemeters in terms of the phantom-related operational quantities Hp(10) and H'(10.0 degrees) was measured for personal and area monitoring systems in mixed high-energy electron and photon radiation fields with energies up to 7 MeV. Using mixed radiation fields composed of different fractions of charged particle and photon fluence, three conditions were produced at the point of measurement: charged particle equilibrium (CPE) (a), a lack (b) and an excess (c) of charged particles relative to the conditions of CPE. Personal and area dosemeters of different types were investigated under conditions (a)-(c). A large variability of the response of the different dosemeter types was observed. The results are presented and discussed.

Air Pollution, Radioactive↗

PubMed1982

The concept of gene transfer-misrepair mechanism of radiation carcinogenesis may challenge the linear extrapolation model of risk estimation for low radiation doses.

The recent demonstration that transformation of cultured cells can be induced by exposure to DNA fragments prepared from normal mouse tissues provides experimental support to the gene transfer-misrepair hypothesis of radiation carcinogenesis. Employing various assumptions with regard to the generation of oncogenic DNA fragments and of cells which are susceptible to incorporate these fragments into their genome, it is predicted that the proposed mechanism implies a non-linear extrapolation model for the calculation of cancer risks caused by very low doses of ionizing radiation of low LET. It also follows from this hypothesis that X- and gamma-radiation delivered at an extremely low dose rate will be less carcinogenic than at high dose rate, in particular where low total doses are concerned. Several aspects of the hypothesis can be verified experimentally by the use of in vitro cultured cell systems.

Cell Transformation, Neoplastic↗

PubMed1978

Relationship between curative radiation therapy of paravertebral tumors and the incidence of radiation myelitis.

The literature about radiation damage to the spinal cord is reviewed and 4 of own cases are presented. It is pointed out that in curative radiation therapy the risk of myelitis that accompanies higher spinal cord doses must be weighed against the therapeutic gains. However, in view of the lack of information about radiation damage to the spinal cord, this may be quite difficult.

Adult↗

PubMed2026

Low-Dose Radiation-Induced Expression of Exosomal miRNAs in the Serum of Medical Radiation Workers.

Objective: Long-term low-dose ionizing radiation may alter genomes and cause diseases. This study examined serum exosomal miRNA differences among radiation-exposed medical workers by work types. Methods: High-throughput sequencing screened serum exosomal miRNAs in diagnostic radiologists, interventional radiologists, and nuclear medicine doctors. qRT-PCR validated differentially expressed miRNAs. Results: 410 differentially expressed miRNAs, including 102 downregulated and 308 upregulated miRNAs, enriched in 15 KEGG pathways. Four miRNAs were validated. miR-30e-5p, miR-155-5p and miR-486-5p differed significantly among groups(P<0.01).The expression levels of these three miRNAs were lower in the nuclear medicine group than in the diagnostic group (0.25±0.05vs3.89±8.62,0.10±0.15vs7.03±15.75,0.37±0.39vs4.46±9.64;Z=3.542,3.335,9.859;P<0.01), whereas miR-155-5p was lower in the interventional group than in the diagnostic group(1.32±2.43vs 7.03±15.75;H=11.889,P=0.003), miR-486-5p was higher(9.54±19.39vs4.46±9.64; H=9.859,P=0.007). All four miRNAs showed higher expression in the 14-31-year work-experience group, and all four also showed age-dependent differences, with miR-30d-5p and miR-486-5p showing the age-related differences (P<0.01). Combined detection of the four miRNAs improved discrimination among occupational categories (AUC=0.784). Multiple linear regression analysis showed that sex was associated with all four miRNAs, whereas work type was associated with miR-30d-5p and miR-155-5p (P<0.05). Conclusion: Serum exosomal miR-30e-5p, miR-155-5p, and miR-486-5p are promising biomarkers for monitoring radiation-induced damage, supporting occupational protection and health management.

exosomes↗

PubMed2003

High-risk Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group Study--TROG 96:07.

PURPOSE: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy was prospectively assessed in a group of patients with high-risk Merkel cell carcinoma (MCC) of the skin. PATIENTS AND METHODS: Patients were eligible if they had disease localized to the primary site and nodes, and were required to have at least one of the following high risk features: recurrence after initial therapy, involved nodes, primary tumor size greater than 1 cm, gross residual disease after surgery, or occult primary with nodes. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks and synchronous carboplatin (area under the curve, 4.5) and intravenous etoposide 80 mg/m2 days 1 to 3 was given in weeks 1, 4, 7, and 10. The median age of the group was 67 (range, 43-86) years, and there were 39 males and 14 females. Involved nodes (stage II) were present in 33 cases (62%). The sites involved were head and neck (22 patients), occult primary (13 patients), upper limb (eight patients), lower limb (eight patients), and trunk (two patients). RESULTS: Fifty-three patients were entered between 1996 and 2001. The median potential follow-up was 48 months. There were no treatment related deaths. The 3-year overall survival, locoregional control, and distant control were 76%, 75%, and 76%, respectively. Tumor site and the presence of nodes were factors that were predictive for local control and survival. Multivariate analysis indicated that the major factor influencing survival was the presence of nodes; however, this was not a significant factor in locoregional control. CONCLUSION: High levels of locoregional control and survival have been achieved with the addition of chemotherapy to radiation treatment for high-risk MCC of the skin. The role of chemoradiotherapy for high-risk MCC warrants further investigation.

Adult↗

PubMed2003

RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database.

PURPOSE: This phase II, open-label, multicenter study assessed the efficacy and safety of the potential radiation enhancer RSR13 plus cranial radiation therapy (RT) in patients with brain metastases. The primary end point was patient survival in comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database (RTOG RPA BMD). PATIENTS AND METHODS: Eligibility criteria were age > or = 18 years, Karnofsky performance score > or = 70, and brain metastases with solid tumor histology. Patients received cranial RT, 30 Gy in 10 fractions of 3 Gy each, preceded by RSR13, 50 to 100 mg/kg intravenously over 30 minutes. Univariate and multivariate comparisons of survival and cause of death were made between class II study patients and RTOG BMD patients. RESULTS: Fifty-seven RPA class II patients were enrolled. With a minimum follow-up of 24 months, the median survival time and 1- and 2-year survival rates were 6.4 months, 23%, and 11% for the RSR13-treated patients compared with 4.1 months, 15%, and 3% for the RTOG BMD patients (P =.0174). In an exact-matched case analysis (n = 38), median survival time for RSR13 patients was 7.3 months versus 3.4 months for the RTOG BMD patients (P =.006). There was a 54% reduction in the risk of death for RSR13 patients (P =.0267). RSR13-related adverse events of greater than or equal to grade 3 toxicity that occurred in more than one patient included hypoxia, headache, anemia, fatigue, hypertension, and intracranial hypertension. CONCLUSION: RSR13 plus cranial RT resulted in a significant improvement in survival, as well as a reduction in death due to brain metastases, compared with class II patients in the RTOG BMD.

Adult↗

PubMed1987

Radiation safety in the nuclear medicine department: impact of the UK Ionising Radiations Regulations.

The practice of nuclear medicine requires integration of radiation safety with patient care and radiopharmaceutical standards. Nationally there was useful discussion in the UK before the Ionising Radiations Regulations and Approved Code of Practice were published, although such consultation had been lacking when the Medicines Act was implemented. Most of the new considerations relating to nuclear medicine stem from Schedule 6 of the Regulations. Generally, the presence of a single patient does not require a controlled area. However, when several patients are present, or radiopharmaceuticals are being prepared prior to injection, a controlled area is required. Classification of workers is not likely to be required in a typical nuclear medicine department in the UK, although most parts of the nuclear medicine department will need to be controlled areas. These include the radiopharmacy, radionuclide dispensary, injection room, and imaging rooms if patients are injected in them. The importance of finger dose measurements is emphasised. Patient wards, however, need not be controlled areas. A particular concern in nuclear medicine was that patients should not need to be admitted to hospital merely to comply with legislation. This is possibly the case and clarification will probably be available when the Notes for Guidance are published. Most procedures in nuclear medicine departments will remain unchanged. Further information is required, however, on patient waiting rooms, handling flood sources, pregnancy, and breast feeding. Within the hospital, detailed and multidisciplinary discussion will need to take place within the forum of the radiation safety committee.

Hospital Departments↗

PubMed2004

The influence of radiation quality on radiation-induced hemolysis and hemoglobin oxidation of human erythrocytes.

Human erythrocytes were exposed to gamma-rays and alpha-particles to assess radiation-induced membrane damage and hemoglobin oxidation and denaturation. With all parameters measured, the alpha-particles proved to be less efficient than the gamma-rays. The time-dependence of hemolysis showed also clear differences: with the gamma-rays the process was faster, reaching saturation after 40-90 min (depending on dose), but with the alpha-particles the final level was attained only after about 3-7 h. Hemoglobin oxidation and denaturation could be measured only after gamma-exposure, but they were negligible with the alpha-particles when comparable doses were applied. These results are interpreted by proposing that OH-radicals, whose yields are smaller with densely ionizing radiation, play a crucial role in the induction of the processes for radiation-induced erythrocyte damage.

Alpha Particles↗

PubMed2002

Report on an interagency workshop on the radiobiology of nuclear terrorism. Molecular and cellular biology dose (1-10 Sv) radiation and potential mechanisms of radiation protection (Bethesda, Maryland, December 17-18, 2001).

The events of September 11, 2001 have focused attention on the possibility of nuclear terrorism, and 1-10 Sv is arguably the dose range of biological interest, since doses in this range both pose a risk of acute effects and are potentially survivable. Because of this interest, a coalition of U.S. government agencies (NCI, DOD, DOE) and the Radiation Research Society convened a workshop in December 2001 "to focus on molecular, cellular and tissue changes that occur [at doses of 1-10 Sv] and potential mechanisms of radioprotection". A draft report of this workshop was posted on the NCI website in February 2002. According to the draft, the workshop was also intended to "determine the research opportunities and resources required [and] develop a research-action plan for further discussion and implementation." Injuries after exposure to ionizing radiation are important to patients with cancer and to populations potentially subject to accidental or intentional exposure. In these populations, partial- or whole-body exposures in the range of 1-10 Sv are possible. The consequences of exposure of limited tissue volumes to doses above 10 Sv have been researched because of their applicability to cancer therapy, while exposure to doses below 1 Sv has been researched because of nuclear fallout and space exploration issues. Except for research aimed at protection of members of the armed forces, the intervening dose range has received relatively little attention. The workshop participants concluded that although we currently have only a limited ability to deal with the consequences of radiation exposures in this range, focused research would have the potential of rapidly expanding such capabilities.

Biomarkers↗

PubMed1986

Radiation dose in investigations of the large bowel. Comparison of radiation doses in examinations of the colon with double-contrast barium enema with the Welin modification and colonoscopy.

Because of the increasing and repeated application of colonoscopy and double-contrast barium enema with the Welin modification in connection with the checking of patients who have been treated for neoplastic polyps, we have found it valuable to examine the amount of radiation that the patients are exposed to in the two kinds of examinations. The radiation dose in the examination of the colon with the Welin modification (35 examinations) and at colonoscopy (114 examinations) was, on an average, 387 and 10 mSv, respectively. Since colonoscopy gives a possibility not only of diagnosis but also of treatment and also exposes the patients to 40 times less radiation than X-ray examination with the Welin modification, we recommend colonoscopy for diagnosis and treatment of neoplastic colonic polyps.

Adolescent↗

PubMed2006

Phase II trial of conformal radiation therapy for pediatric patients with craniopharyngioma and correlation of surgical factors and radiation dosimetry with change in cognitive function.

OBJECT: A Phase II trial of conformal radiation therapy (CRT) for craniopharyngioma was conducted to determine whether the irradiated volume could be safely reduced to decrease effects on cognitive function. METHODS: Between July 1997 and January 2003, 28 pediatric patients (median age 7.3 +/- 4.12 years) received CRT in whom doses (54-55.8 Gy) were administered to the gross tumor volume (solid and cystic components) surrounded by a 1-cm clinical target volume margin. Patients were evaluated serially with neuropsychometric testing. Statistical analyses were performed to determine the effect of clinical factors and radiation dosimetry on intelligence quotient (IQ). The median follow-up period was 36.6 months (range 24.4-80 months). The estimated 3-year progression-free survival rate was 90.3 +/- 7.3%. Three patients experienced local disease progression. Cognitive outcome for patients was adversely affected by the following factors: age younger than 7.4 years (p = 0.001), an interval between symptoms and diagnosis of more than 73 days (p = 0.06), more extensive surgery (p = 0.014), multiple surgical procedures (p = 0.002), diabetes insipidus (p = 0.02), hydrocephalus at diagnosis (p = 0.009), a cerebrospinal fluid shunt (p = 0.005), shunt revisions (p = 0.01), Ommaya reservoir laterality (p = 0.005), and cyst aspirations (p = 0.02). The percentage of total brain, supratentorial brain, or left temporal lobe volumes receiving a dose in excess of 45 Gy had a significant impact on longitudinal IQ. CONCLUSIONS: The use of CRT with a 1-cm margin for clinical target volume results in tumor control equivalent to that achieved using conventionally planned radiation therapy. Surgical morbidity and a volume-receiving dose more than 45 Gy are factors affecting longitudinal IQ after CRT in patients treated for craniopharyngioma.

Adolescent↗

PubMed2002

Behavioral consequences of radiation exposure to simulated space radiation in the C57BL/6 mouse: open field, rotorod, and acoustic startle.

Two experiments were carried out to investigate the consequences of exposure to proton radiation, such as might occur for astronauts during space flight. C57BL/6 mice were exposed, either with or without 15-g/cm2 aluminum shielding, to 0-, 3-, or 4-Gy proton irradiation mimicking features of a solar particle event. Irradiation produced transient direct deficits in open-field exploratory behavior and acoustic startle habituation. Rotorod performance at 18 rpm was impaired by exposure to proton radiation and was impaired at 26 rpm, but only for mice irradiated with shielding and at the 4-Gy dose. Long-term (>2 weeks) indirect deficits in open-field activity appeared as a result of impaired experiential encoding immediately following exposure. A 2-week recovery prior to testing decreased most of the direct effects of exposure, with only rotorod performance at 26 rpm being impaired. These results suggest that the performance deficits may have been mediated by radiation damage to hippocampal, cerebellar, and possibly, forebrain dopaminergic function.

Animals↗

PubMedDate not supplied

[A possibility to predict the severity of individual damage following the exposure to supralethal radiation dosage. Prediction by early radiation response ].

The experiments on dogs and monkeys have shown that the severity of radiation sickness following the exposure to supralethal radiation doses can be predicted by early response of an individual. For such prediction, the most informative criteria include general severity of clinical manifestations during primary radiation response and evaluated within a few post-damage hours, the degree of tension in cardiac rhythm control, the cortisol level, the endocrine status index.

Animals↗

PubMed2001

Radiation exposure of civilian airline crew members and associated biological effects due to the atmospheric ionizing radiation environment.

A study, currently in progress, on the radiation exposure and the associated biomedical effects due to the atmospheric ionizing radiation environment for the Italian civilian aviation flight personnel is sketched. After a presentation of the considered data sources, a description of the cohort is given, in terms of criteria for eligibility, and cohort construction, size and composition. Then the protocol for the Italian study is presented: the various ways of investigating the exposure and the health status of past and currently employed aircrew members and follow-up procedures are shown. An overview is given of the data management and processing philosophy with regards to flight routes, radiation dose evaluation along the flight path and exposure matrix building, as adopted in the Italian study. Potential side studies of interest are also shown.

Aerospace Medicine↗

PubMedDate not supplied

[Radiation loading, radiation-induced diseases and suicide values in a region adjacent to a nuclear testing ground].

Radiation effects on the population health at a territory adjacent to the Semipalatinsk nuclear testing grounds were studied. Immunosuppression and suppression of nonspecific defense factors, induced by radiation from the testing grounds, determine the extension of physiological lability range, accelerate the natural involution processes, and create psychoemotional stress. The totality of radiation-induced general physiological effects with pronounced dose dependence of their incidence and intensity represents a co-factor of suicide.

Body Burden↗

PubMed1976

Radiation nephritis. Chronic changes following moderate doses of radiation.

Experimental radiation nephritis in the rat is the result of progressive injury involving glomeruli and tubules. Vascular damage plays litter or no role in the initial stages although arterial necrosis and thrombosis develop in the late stages. The radiation nephritis is essentially a degenerative process and the inflammatory reaction, if any, appears to be secondary to necrosis. Within the range employed in this and in previous experiments (1,500 to 10,000 rads), the nature of changes is the same regardless of the dose; large doses of radiation merely accelerate and aggravate the process. During the "latent'' phase there are progressive ultrastructural alterations which eventually become evident by light microscopy.

Animals↗

PubMedDate not supplied

Radiation bronchitis in lung cancer patient treated with stereotactic radiation therapy.

We report a case of chronic radiation bronchitis that developed in a patient with lung cancer treated with fractionated stereotactic radiation therapy. A 73-year-old woman with a medically inoperable T1N0M0 adenocarcinoma of the lung was treated with stereotactic radiation therapy. By using eight non-coplanar ports, 50 Gy/5 fractions was delivered in two weeks. At four weeks, a partial response was obtained with no acute adverse reaction. She developed severe cough at six months. Fiberoptic bronchoscopy revealed thick circumferentially coated bronchial mucosa in close proximity to the tumor site. At 12 months, follow-up study confirmed marked stenotic change in the B6 segmental bronchus without tumor progression.

Adenocarcinoma↗