Radiation research
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Two human melanoma cell lines, one radioresistant (SK-MEL-3) and one radiosensitive (HT-144), and a normal human fibroblast line (AG1522) were evaluated for thermoradiosensitization of low-dose-rate irradiation by concurrent mild hyperthermia (39-41 degrees C). None of the cell lines expressed chronic thermotolerance during heating at 39-41 degrees C. ⋯ The SK-MEL-3 cells, which were the most resistant to radiation and demonstrated the greatest repair of sublethal damage (SLD) during low-dose-rate irradiation, had the greatest thermal enhancement of radiosensitivity, while the HT144 cells, which were the most sensitive and expressed little repair of SLD during low-dose-rate irradiation, had the smallest thermal enhancement of radiosensitivity. These data show that concurrent mild hyperthermia during low-dose-rate irradiation may be most efficacious in radiation-resistant tumor cells which express resistance through an enhanced capacity for repair of SLD.
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In an earlier study using cell sorting techniques to define the radiation survival response of asynchronous Chinese hamster V79-171 cells more accurately, we found evidence of substructure in the response at low dose. In the present work we have attempted to show that this substructure arises from the subpopulations of sensitive (G1, G2 phase) and resistant (late S phase) cells which are present in asynchronously dividing cultures but which are not resolved by conventional survival assays. Partially synchronized cells were produced by exposure to 1 mM hydroxyurea for 12 h and were harvested 15 min later, yielding a population of viable cells at or just beyond the G1/S-phase boundary. ⋯ The average of repeated measurements of the radiation survival response of asynchronous cells again showed a significant difference (P = 0.002 to 0.009) between the alpha and beta values evaluated from the data for the low-dose range, 0-2.8 Gy, and the high-dose range, 2.8-14 Gy. For G1/S-phase cells, however, there was no significant difference between the values of alpha and beta for the low-dose and high-dose ranges (P > 0.5). The results thus support the hypothesis that the observed substructure in the asynchronous response is due to resolution of subpopulations of different radiosensitivities, and they illustrate the advantage of the cell sorter assay for accurate measurements of cell survival, particularly at low dose.
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High-resolution measurements of the survival of asynchronous Chinese hamster V79-379A cells in vitro after single doses of X rays (0.01-10.0 Gy) and neutrons (0.02-3.0 Gy) were made using a computerized microscope for locating and identifying cells (Palcic and Jaggi, Int. J. Radiat. ⋯ Further data suggest that this phenomenon is unlikely to be due to a subpopulation of X-ray-sensitive cells determined either genetically or phenotypically by distribution of the population within the cell cycle. The existence of low-dose sensitivity also appeared to be independent of dose rate in the range 0.016-1.7 Gy min-1. A possible explanation of these results is that the phenomenon reflects "induced repair" or a stress response: low doses in vitro (or low doses per fraction in vivo) are more effective per gray than higher doses because only at the higher doses is there sufficient damage to trigger repair systems or other radioprotective mechanisms.
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The effects of regional hyperthermia (42 degrees C for 70 min) on the antitumor activity of melphalan were examined in athymic mice bearing melphalan-resistant human rhabdomyosarcoma (TE-671 MR) xenografts growing in the right hind limb, and results were compared with similar studies of melphalan-sensitive (TE-671) parent xenografts. Melphalan alone at a dose of 36 mg/m2 (0.5 of the 10% lethal dose) produced growth delays of 4.1 to 10.2 days in TE-671 MR xenografts and 21.8 to 28.7 days in TE-671, respectively. Hyperthermia alone produced growth delays of 0.9 days in TE-671 MR xenografts and 0.8 days in TE-671. ⋯ Hyperthermia plus melphalan did not result in a higher tumor-to-plasma melphalan ratio compared with treatment with melphalan alone in either TE-671 MR or TE-671 xenografts. These studies suggest that heat-induced alterations in tumor glutathione or melphalan levels are not responsible for the increase in melphalan activity produced by hyperthermia. Combination therapy with melphalan plus regional hyperthermia offers promise for treatment of melphalan-resistant neoplasms.
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Beagle dogs that were part of a life span study of the effects of low-level ionizing radiation during development were evaluated for the incidence of skin neoplasia and solar dermatosis. A total of 991 dogs up to 14 years of age were examined. The dogs were housed in gravel-based, outdoor pens with doghouses in a high-altitude, high-sunshine level environment. ⋯ Whole-body gamma-radiation exposures were delivered at one of three prenatal or three postnatal ages up to 1 year of age. There appeared to be an increased risk for hemangiosarcomas and squamous cell carcinomas in dogs with solar dermatosis and given gamma-ray exposures at 1 year of age. This suggests an interaction between exposures to ionizing and ultraviolet radiation.