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Radiation-induced cell transformation: transformation efficiencies of different types of ionizing radiation and molecular changes in radiation transformants and tumor cell lines.

This study aims to compare the efficiencies of 5.4 keV soft X-rays, alpha-particles, and gamma-rays in transforming C3H 10T1/2 cells and to assess the sequence of cellular and molecular changes during the process of radiation-induced transformation of Syrian hamster embryo (SHE) cells. The somewhat more densely ionizing soft X-rays are more effective than gamma-rays both for cell inactivation and cell transformation. The relative biological effectiveness (RBE) appears to be independent of dose; it is approximately 1.3 for either end point. The RBE of alpha-particles versus gamma-rays, on the other hand, increases with decreasing dose; the dose dependence is somewhat more apparent for cell transformation than for cell inactivation. SHE cells transformed by different types of ionizing radiation and related tumor cell lines isolated from nude mice tumors were found to have a distinct growth advantage compared to primary SHE cells, documented by higher plating efficiencies, shorter doubling times, and higher cloning efficiencies in semisolid medium. Most transformed and tumor cell lines that were investigated have elevated mRNA levels for the H-ras gene, some of them show restriction fragment length polymorphisms of the H-ras gene, and some exhibit a substantially amplified c-myc gene. In a sequence analysis of the Syrian hamster H-ras gene of eight tumor cell lines from radiation transformants, we have not found any mutation in codons 12, 13, 59, 61, nor in the flanking regions of these codons. The transformed and tumor cell lines tend to have lower chromosome numbers than primary SHE cells.

Alpha Particles↗

[Results of the studies on radiation ecology and radiation biology at the Institute of Biology of Komi Science Center of Ural division of Russian Academy of Science (on 40th anniversary of the Department of Radiation Ecology)].

Information about the foundation and history of the Radiation Ecology Department and results of the researches on the effect of increased background radiation level on plant and animal populations, migration of radionuclides in natural biocoenosies with increased radiation level are presented.

Academies and Institutes↗

In vitro generation of cytotoxic lymphocytes against radiation- and radiation leukemia virus-induced tumors. III. Suppression of anti-tumor immunity in vitro by lymphocytes of mice undergoing radiation leukemia virus-induced leukemogenesis.

Adult C57BL/6 mice exposed to fractionated irradiation or inoculated with the radiation leukemia virus (RadLV), develop high incidence (80-100%) of lymphatic leukemias within 3-6 mo. RadLV-induced lymphomas can elicit cytotoxic responses in vitro in lymphocytes of preimmunized syngeneic mice, a reaction that is dependent on the expression of membrane-associated viral antigenicity. As soon as 5 d after RadLV inoculation, and during the entire leukemogenic process, suppressor T cells are detectable in the spleen that are capable of specifically abrogating generation of syngeneic anti-tumor cytotoxic cells in vitro. Mice exposed to fractionated x irradiation do not develop suppressor cells and their splenocytes may be stimulated in vitro to generate cytotoxicity toward RadLV-induced leukemias. These findings suggest that although RadLV has been isolated from radiation-induced leukemias, x-ray- and RadLV-induced leukemogenesis do not seem to involve a common viral etiology, and that induction of suppressor cells during RadLV leukemogenesis may be essential for tumor progression.

Animals↗

Radiation oncology training in the United States: report from the Radiation Oncology Resident Training Working Group organized by the Society of Chairman of Academic Radiation Oncology Programs (SCAROP).

PURPOSE: In response to the major changes occurring in healthcare, medical education, and cancer research, SCAROP addressed issues related to post-graduate education that could enhance existing programs and complement the present system. METHODS AND MATERIALS: SCAROP brought together a Working Group with a broad range of representatives organized in subcommittees to address: training, curriculum, and model building. RESULTS: The Working Group emphasized the importance of training physicians with the necessary clinical, scientific, and analytical skills, and the need to provide expert radiation oncology services to patients throughout the United States. Opportunities currently exist for graduates in academic medicine, although there may be limited time and financial resources available to support academic pursuits. CONCLUSIONS: In the face of diminishing resources for training and education and the increased scope of knowledge required, a number of models for resident training are considered that can provide flexibility to complement the present system. This report is intended to initiate dialogue among the organizations responsible for radiation oncology resident education so that resident training can continually evolve to meet the needs of cancer patients and take advantage of opportunities for progress through innovative cancer care and research.

Curriculum↗

Effects of ultraviolet radiation on respiration and growth in radiation-resistant and radiation-sensitive strains of Escherichia coli B.

Ultraviolet (UV) irradiation at 254 nm causes different respiration and growth responses in log-phase cultures of Escherichia coli B/r and B(s-1). These differences are correlated with the ability and inability, respectively, of these bacterial strains to repair UV-induced lesions in deoxyribonucleic acid (DNA). After irradiation, B(s-1) cells (radiation-sensitive) exhibit uncoupling of growth and respiration; growth and synthesis cease, whereas respiration continues. B/r cells (radiation-resistant) grown on glycerol exhibit severe temporary inhibition of growth and respiration after UV, and the coupling of these two processes is maintained, except at a very high UV dose. Inhibition begins at about the time DNA synthesis resumes and continues for a period of time that is dependent upon dose. Glucose-grown cells do not exhibit severe respiratory, growth, and synthetic inhibitions; these processes remain coupled in the cells during the postirradiation period. Photoreactivation treatment delays uncoupling of growth and respiration in B(s-1) and prevents inhibition of respiration and growth in B/r. These results indicate that the postirradiation responses result from the presence of pyrimidine dimers in DNA. Ultraviolet irradiation of B/r and B(s-1) cells results in an accumulation of adenosine triphosphate by 30 min after UV. This accumulation decreases with time and does not appear to be related to the inhibition of respiration in glycerol-grown B/r cells. The results on B/r are interpreted in terms of a control mechanism for reestablishment of a balance among macromolecules in the irradiated cells so as to provide them with the potential to survive. The specific steps in such a reestablishment of balance appear to depend upon the substrate oxidized. In B(s-1) cells, which cannot repair UV-induced damage in DNA, some control mechanism that coordinates cellular processes may be inactivated.

Adenosine Triphosphate↗

Comparison of the Radiation Therapy Oncology Group and American Joint Committee on Cancer staging systems among patients with non-small cell lung cancer receiving hyperfractionated radiation therapy. A report of the Radiation Therapy Oncology Group protocol 83-11.

Since 1973, the Radiation Therapy Oncology Group (RTOG) has staged and stratified patients in non-small cell lung cancer (NSCLC) protocols according to the RTOG staging system. In 1985, the American Joint Committee on Cancer (AJCC) revised its lung cancer staging system, with the principle differences from the RTOG system being the staging of involvement of the chest wall and of contralateral mediastinal and hilar lymph nodes. To determine if the AJCC system discriminated outcome differently than the RTOG system in a nonoperative series, all 850 evaluable patients treated with hyperfractionated radiation therapy (RT) on the RTOG protocol 83-11 were restaged by the AJCC system. There was 67% agreement in patient distribution between the following comparable stages in each system: RTOG Stage II/AJCC Stage II; RTOG Stage III/AJCC Stage IIIA; and RTOG Stage IV/AJCC Stage IIIB. Both systems successfully predicted for survival (P less than 0.001), although the RTOG staging was more discriminating (relative risk ratios, 1.59 versus 1.38). Among the 507 favorable patients (those with less than or equal to 5% weight loss and Karnofsky performance status [KPS] of 70 to 100), the RTOG staging was also more predictive (P = 0.004 versus P = 0.01). When RTOG Stage III (462 patients) was divided into those without contralateral mediastinal or hilar adenopathy (AJCC Stage II/IIIA) and those with (AJCC Stage IIIB), a significant survival (P = 0.0001) was noted with 2-year survival rates of 26% versus 4%, respectively. When AJCC Stage IIIA (348 patients) was divided into the patients without chest wall invasion (RTOG Stage II/III) and those with (RTOG Stage IV), a difference in 2-year survival of 22% versus 10% was observed (P = 0.002). Although both staging systems independently predict for survival, a fusion of both staging systems is the most discriminating of outcome. Future nonoperative studies in locally advanced NSCLC should stratify for contralateral nodal involvement (per AJCC staging) and chest wall invasion (per RTOG staging).

Carcinoma, Non-Small-Cell Lung↗

Health-related quality-of-life after external beam radiation therapy for localized prostate cancer: intensity-modulated radiation therapy versus conformal radiation therapy.

We compared health-related quality-of-life (HRQL) after intensity-modulated radiotherapy (IMRT) with statuses obtained after old and new protocols of three-dimensional conformal radiation therapy (3DCRT) for localized prostate cancer. We measured the general and disease specific HRQL using the MOS 36-Item Health Survey (SF-36), and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI), respectively. IMRT resulted in similar profiles of general and disease-specific HRQL to two other methods within the first year after treatment. Moreover, IMRT gave rise to comparable urinary, intestinal and sexual side effects despite the high dose of radiation applied.

Aged↗

Tirapazamine, Cisplatin, and Radiation versus Fluorouracil, Cisplatin, and Radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02).

PURPOSE: To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial. PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost). RESULTS: Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79%; P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms. CONCLUSION: Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial.

Adult↗

[Radiation monitoring in the area of metallic dental replacement during cobalt 60 gamma radiation and in electron radiation of oral tumors].

In the radiotherapy of malignant tumors of the oral cavity, the exact distribution of radiation dosage in the neighborhood of metallic dental replacement has been uncertain so far. Many authors therefore asked that crowns and bridges be removed before radiotherapy. By means of lithium fluoride thermo-luminescence dosimetry, punctate measurements of doses are possible for the first time. In view of the dose values obtained, removal of metallic dental replacement before the beginning of radiotherapy as a prophylactic measure to prevent radioosteomyelitis appears not to be necessary.

Cobalt Radioisotopes↗

Education and training for radiation scientists: radiation research program and American Society of Therapeutic Radiology and Oncology Workshop, Bethesda, Maryland, May 12-14, 2003.

Current and potential shortfalls in the number of radiation scientists stand in sharp contrast to the emerging scientific opportunities and the need for new knowledge to address issues of cancer survivorship and radiological and nuclear terrorism. In response to these challenges, workshops organized by the Radiation Research Program (RRP), National Cancer Institute (NCI) (Radiat. Res. 157, 204-223, 2002; Radiat. Res. 159, 812-834, 2003), and National Institute of Allergy and Infectious Diseases (NIAID) (Nature, 421, 787, 2003) have engaged experts from a range of federal agencies, academia and industry. This workshop, Education and Training for Radiation Scientists, addressed the need to establish a sustainable pool of expertise and talent for a wide range of activities and careers related to radiation biology, oncology and epidemiology. Although fundamental radiation chemistry and physics are also critical to radiation sciences, this workshop did not address workforce needs in these areas. The recommendations include: (1) Establish a National Council of Radiation Sciences to develop a strategy for increasing the number of radiation scientists. The strategy includes NIH training grants, interagency cooperation, interinstitutional collaboration among universities, and active involvement of all stakeholders. (2) Create new and expanded training programs with sustained funding. These may take the form of regional Centers of Excellence for Radiation Sciences. (3) Continue and broaden educational efforts of the American Society for Therapeutic Radiology and Oncology (ASTRO), the American Association for Cancer Research (AACR), the Radiological Society of North America (RSNA), and the Radiation Research Society (RRS). (4) Foster education and training in the radiation sciences for the range of career opportunities including radiation oncology, radiation biology, radiation epidemiology, radiation safety, health/government policy, and industrial research. (5) Educate other scientists and the general public on the quantitative, basic, molecular, translational and applied aspects of radiation sciences.

Curriculum↗