[en] Published in summary form only

[en] The radiosensitizing effects of misonidazole and SR 2508 (1 mg/g) were compared on a human melanoma (Na11) containing 85% hypoxic cells transplanted into nude mice. For both drugs, the enhancement ratios (ER) were 1.7 after immediate plating and 2.1 after delayed plating. This difference in ERs is related to a lack of PLD repair in tumors in the presence of the sensitizer. The effect of misonidazole was also investigated in another human melanoma (Be11) containing 40% hypoxic cells. After immediate plating, the Er was similar to that observed with the Na11 tumor (1.7)m but PLD repair was not reduced. A comparative analysis of the influence of misonidazole on the response (survival curve - PLD repair) of Na11 melanoma to different ionizing radiations was attempted

[en] Split dose and fractionated γ-rays experiments have been performed on a human melanoma transplanted into nude mice using an in vitro colony assay. Repair of potentially lethal damage observed after a single dose of 20 Gy was found to no longer occur when 7 daily doses of 2.5 Gy were administered. In split-dose experiments, the increase in survival level probably can not be explained by repair of sublethal damage. When a single high dose of radiation is administered a certain reoxygenation is observed; however, there is no reoxygenation when low radiation doses are delivered daily

[en] One hundred and one published survival curves for 92 human cell lines (including 64 tumor lines) have been analyzed in terms of several parameters that are supposed to characterize cell radiosensitivity. Values for n, Do, alpha and beta (from the linear quadratic model), D (Mean Inactivation Dose), and survivals at 2 Gy and 8 Gy have been obtained for each curve. It was found that: I. the initial part of the survival curve is specific to the corresponding cell line; II. this initial part is well characterized by the parameters alpha and D, the values of which can be used to compare intrinsic radiosensitivity among human cell lines; III. human tumor cell line radiosensitivity (expressed in terms of alpha, D and survival at 2 Gy) reflects the clinical radioresponsiveness of the tumors from which the cell lines are derived. Thus, cells from tumors with low radioresponsiveness (melanomas and glioblastomas) are the less radiosensitive. Furthermore, the range of survival at a dose of 2 Gy is broad enough to account, in large measure, for observed differences in clinical tumor radioresponsiveness

No abstract available

No abstract available

[en] Metastatic lymph nodes of EMT6 tumors growing in athymic nude mice were used at different sizes and their radiosensitivity was tested with the in vitro colony method. Following the administration of 1250 rad, the surviving fraction in air-breathing animals was found to be dependent on the size of these metastases, expressed either in weight or in cell yield per lymph node. The increasing radioresistance with increase in size was probably due to the presence of higher hypoxic fraction in big nodes (0.43 in nodes weighing more than 320 mg vs 0.10 in nodes less than 80 mg). The surviving fraction after irradiation in acutely hypoxic conditions (asphyxiated animals) or in fully oxygenated ones (in vitro) was not size dependent. Great variations were observed in the radiosensitivity of small metastatic nodes, whereas bigger metastases had a more homogeneous response. The effect of the radiosensitizer misonidazole at a dose of 0.3 mg/g was assessed on lymph node metastases of different sizes. In the presence of the drug, the survival level of big and small metastases differed by a factor of 2.2, as opposed to 4.3 in untreated metastases. This suggests that the radiosensitization is less pronounced in metastases containing a smaller hypoxic fraction

[en] A statistical analysis has been performed on a set of 59 published survival curves of human cell lines. Six fibroblast cell lines derived from patients free of genetic disorders and 36 tumor cell lines were used in this study. Using the linear quadratic (L-Q) model, which provides an overall adequate fitting, especially in the low dose range, we show that great variations in radiosensitivity exist among cell lines. In the low dose range (approx. = 2 Gy), these variations cannot be explained on the mere basis of technical factors. A correlation is found between the 95% tumor control dose and the mean surviving fraction at 2 Gy for a given cell type. Higher radiosensitivity is accompanied by lower tumor control dose (TCD 95%). This correlation suggests that the moderate radiocurability of certain tumors can be partially explained by the intrinsic radiosensitivity of relevant tumor cells and in particular by a high surviving fraction at 2 Gy

[en] In order to reduce the radioresistance due, among others, to hypoxia in solid tumors, research on radiosensitizers (especially the electron-affinic sensitizers) has been active for many years. The radiosensitization efficiency and the cytotoxic and transforming effects of a great number of substances was first studied in vitro. Then two drugs, metronidazole and misonidazole, were tested especially in vivo in animals; this research concerned their effect both on tumors and on normal tissues. After presenting an overwiew of the experimental results, we summarize the preliminary results of the first clinical trials with misonidazole. The general tolerance to this drug is now well known: its local influence on tumors and also normal tissues radiosensitivity is the object of most of the present clinical trials

[en] A study has been made of the influence of ionizing radiations on the life span of non-transformed HF 19 human fibroblasts in vitro. The life span of surviving clones was found to be reduced when the cells had received two or three doses of 6 Gy separated by an interval of 15 doublings. In addition, this reduction in life span was greater when the cells were older at the time of irradiation. (author)