[en] The main purpose was to provide additional information on two questions; (1) How does the radiosensitising effect of oxygen depend on oxygen concentration and cellular age, and (2) How does the radiosensitising effect of hypoxic cell sensitisers depend on concentration of sensitiser and cellular age. The general conclusions reached were as follows. The radiosensitising effect of oxygen on NHIK 3025 cells in G1 increased with increasing dose of radiation. For cells irradiated in S oxygen acted as a dose-modifying agent. For small doses of radiation the sensitising effect of oxygen was weaker for cells irradiated in G1 than for cells irradiated in S. The capacity of NHIK 3025 cells to repair sublethal damage after irradiation under extremely hypoxic conditions was low or even lost (even though the cells were subsequently incubated under aerobic conditions). The radiosensitising effect conferred by TMPN, diamide and misonidazole on NHIK 3025 cells was higher at high doses of radiation than at small doses of radiation (except for the dose-modifying radiosensitisation of cells in S by misonidazole). This observation supports arguments for using high dose fractions in fractionated radiotherapy where such chemicals are involved. (JIW)

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[en] Spleen colony-forming stem cells of the bone marrow of mice (CFU) have been used as an in vivo test system for toxic and radiosensitizing effects of misonidazole. The cells were irradiated in vivo in the donors before they were suspended and injected i.v. into recipients. Hypoxic conditions were achieved by killing the donors 20 min before irradiation. A drug dose in donors of 1.0 mg/g body wt (ca 1200μg/ml in serum) was found to be weakly toxic over an exposure time of 50 min under hypoxic conditions. The radiosensitizing effect at this concentration was found to be about the same as the full effect of oxygen. (author)

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[en] The radiosensitizing effect of the chemotherapeutic drug cis-dichlorodiammineplatinum(II) (cis-DDP) was tested on human NHIK 3025 cells cultivated in vitro. cis-DDP was found to exert a radiomodifying effect under hypoxic but not under aerobic conditions. These results confirm that cis-DDP may act as a radiosensitizer of hypoxic cells; however, the radiosensitizing effect was seen only at concentrations of cis-DDP having a considerable cytotoxic activity, and for practical reasons concerning survival level the highest drug concentration that was investigated was 15 microM at 37⁰C. The radiosensitizing effect was of a dose-modifying type and with a dose-modifying factor (DMF) of 1.2 at 15 microM in hypoxic cells. The radiosensitizing as well as the cytotoxic effect of cis-DDP was found to be strongly temperature dependent. Isoeffect doses of cis-DDP was reduced with a factor of 3 at 22 as compared to 37⁰C. We also found that hypoxic cells were less sensitive to cis-DDP than cells treated in the presence of oxygen. To test the correlation between cytotoxicity and radiosensitization on the one hand and cellular uptake of cis-DDP on the other, cell-associated Pt was measured by atomic absorption spectroscopy. From these studies the cytotoxicity of cis-DDP at 22 and 37⁰C under aerobic conditions was found to be the same as long as the amount of cell-associated Pt (i.e., the cellular uptake) was the same. However, whether the cells were treated under hypoxic or aerobic conditions, the cellular uptake of Pt was the same. While the radiosensitizing effect was present at 37 and at 40⁰C, no such effect could be found at 22⁰C

[en] Human cells of line NHIK 3025 were irradiated suspended in growth medium (E2) in absence and presence of diamide under aerobic and extremely hypoxic (<4 ppm O₂) conditions. A sensitizing effect of diamide was found for doses exceeding 8 Gy (800 rad) on cells irradiated under extremely hypoxic conditions in presence of diamide of concentration 200 μM, whereas no significant effect was observed for 20 μM. (author)

[en] The photodesensitizing effect of haematoporphyrin (HP) on human cells of the established line NHIK 3025 has been studied. Fluorescence measurements show that HP is bound to these cells. Serum proteins also bind HP, and the presence of 10% human serum during incubation with HP (3 x 10^-4M) reduces the cellular uptake of HP by 75% or more. The photosensitized inactivation is enhanced when the cells are suspended in D₂0-buffer during irradiation. This indicates that singlet oxygen is involved in the inactivation. Two findings indicate that the photoinduced damage is repairable: firstly, the fraction of cells surviving a given light dose decreases with decreasing irradiation temperature, and secondly, the survival curves have a shoulder at low exposures of light. (author)