No abstract available

[en] Cell cycle kinetics and radiation response under hypoxic conditions were analyzed with human cells of the line NHIK 3025. The cells were either kept on continuous exponential growth by frequent reculturing, of went through log and plateau phase for each passage (recultured weekly). The cell cycle time for weekly recultured populations in early log phase was shorter than for cells in continuous exponential growth. Cells in continuous exponential growth were more sensitive to radiation than cells in log phase. The difference in sensitivity was not due to partial synchrony of weekly recultured populations. (Auth.)

[en] The effect of X-irradiation on the cell cycle progression of synchronized populations of the human cell line NHIK 3035 has been studied in terms of the radiation-induced delay of DNA replication and cell division. Results were obtained by flow cytometric measurements of histograms of cellular DNA content and parallel use of conventional methods for cell cycle analysis, such as pulse labelling with (³H) thymidine and counting of cell numbers. The two sets of methods were generally in good agreement, but the advantages of employing two independent techniques are pointed out. Irradiation was found to have a minor influence on DNA replication. As compared with unirradiated populations, half-completed DNA replication was 20-30 min delayed in populations given 580 rad in mid-G₁ or 290 rad in early S. Cell cycle progression was markedly delayed in G₂. The sensitivity induction of this delay was 0.6 min/rad for populations irradiated in mid-G₁, and 1.4 min/rad for populations irradiated in early S. (author)

No abstract available

[en] The effect of single dose irradiation on the proliferation kinetics in a human malignant melanoma grown in the athymic mutant nude mouse was analysed. DNA-histograms were obtained with flow cytofluorometry. Percentage labelled mitoses curves were established by the use of conventional autoradiographic techniques. Changes in the fraction of clonogenic cells with time after irradiation were measured in vitro in soft agar. In non-irradiated tumours the fraction of cells in G₁/G₀, S and G₂+M was 66, 21 and 13 per cent respectively. The median duration of G₁, S, G₂, M and Tsub(c) was 19.0 h, 13.3 h, 5.0 h, 1.0 h and 41.1 h, respectively. The growth fraction was calculated as 0.66 and the cell loss factor as 0.67. The growth fraction was increased after irradiation and the cell cycle time reduced, due to a shortening of G₁. These effects were dose dependent and decreased with time after exposure, but were still present after the tumours had resumed a continuous volume growth. The rate of volume growth was slower for irradiated tumours than for non-irradiated tumours of the same size, due to a larger cell loss factor for the former. (Auth.)

[en] The anti-melanoma antibody 9.2.27 localizes to melanoma cells when administered i.v. to melanoma patients, but high doses of this antibody alone have no specific cytotoxic effect in vivo. To determine whether radiolabeled antibodies would exhibit specific antimelanoma cytotoxicity in vitro, cell survival curves were established for NCl-N892 human melanoma cells treated with ¹²⁵I-labeled 9.2.27 monoclonal antibody. The binding capacity per cell was 5 X 10(5) molecules of 9.2.27 immunoglobulin G, and the association constant of binding was 10(10) M-1. Antibody preparations with specific radioactivities of 9-80 microCi/micrograms were used. Colony-forming ability after in vitro exposure to ¹²⁵I-9.2.27 was determined by a 1-h antibody incubation at saturating concentrations, washing, and cell freezing for various exposure durations. Colony survival was dose dependent, varying with the radioactivity per cell and the exposure time. The survival curves demonstrated no shoulder effect and had a 37% incremental survival dose of 0.5-0.9 X 10(5) decays/cell. Selective killing of melanoma cells was demonstrated in experiments where NCl-N417 lung cancer cells were mixed with the melanoma cells prior to antibody treatment. The NCl-N417 cells did not express the melanoma-associated antigen, were more sensitive to conventional external irradiation than were the melanoma cells, and could easily be distinguished from them by different growth morphology. In spite of a growth advantage for the melanoma cells in the clonogenic assay, the antigen-negative lung cancer cells selectively survived the treatment and were the only surviving cells after 15 days of exposure

[en] The radiolabeled anti-T cell antibody T¹⁰¹ can be used for specific tumor localization, but unlabeled T¹⁰¹ produces limited cytotoxicity in patients. We studied the in vitro cytotoxic effects of T¹⁰¹ labeled with ¹²⁵I, a radionuclide known for its short-range, high-linear-energy electrons. We showed that ¹²⁵I-T¹⁰¹ could be readily prepared at high specific activity with high immunoreactivity. Human malignant T cell lines HUT 102, MOLT-4, and HUT 78 were found to differ in the number of T65 determinants (the antigen recognized by T¹⁰¹) and the sensitivity to external x-ray radiation, which were of significance for the cytotoxicity of ¹²⁵I-T¹⁰¹ in vitro. The cytotoxic effects of ¹²⁵I-T¹⁰¹ were also found to be dose dependent and increased with exposure time under frozen conditions. As controls, unlabeled T¹⁰¹ had no cytotoxic effect, while free Na ¹²⁵I or the ¹²⁵I-labeled irrelevant antibody 9.2.27 exerted minor cytotoxicity. In HUT 102 and MOLT-4, more than 3 logs cell killing was achieved within four weeks. Because considerable cytotoxicity was demonstrated in vitro by ¹²⁵I-T¹⁰¹ on T65-positive malignant cells, and because low-dose ¹¹¹In-T¹⁰¹ can be used successfully for tumor localization, future trials using ¹²⁵I-T¹⁰¹ at high specific radioactivity may improve therapeutic results in patients with T65-positive malignancies

No abstract available

[en] Conjugates of monoclonal antibodies with radioactive isotopes, drugs or toxins have great potential for specific radiolocalization and inactivation of tumor cells. Because the conjugation procedure may adversely alter the antibody, quality control procedures must be applied to determine important characteristics of the conjugated antibody. One such property is how much of the conjugated antibody is able to bind to the relevant antigen. Based on theoretical considerations, we have developed a binding assay for radiolabeled monoclonal antibodies in which the fraction of immunoreactive antibody is determined by linear extrapolation to conditions representing infinite antigen excess. This ensures that the true value of the immunoreactive fraction is obtained, as opposed to the apparent immunoreactive fraction determined under conditions of limited antigen excess. The described assay is based on a double-inverse plot of the binding data which may be considered a modification of the Lineweaver-Burk plot. We established the method using ¹²⁵I- and ¹¹¹In-labeling of the 2 monoclonal antibodies T101 and 9.2.27 which currently are undergoing radioimaging trials at the National Cancer Institute. For properly performed conjugation procedures, immunoreactive fractions of about 0.9 were obtained, but a prolonged chloramine-T reaction for ¹²⁵I-labeling resulted in an immunoreactive fraction of only 0.6. Due to its principle of determining binding at infinite antigen excess, the present method is quite insensitive to variation in the actual amounts of cells and antibody used, as well as the incubation time. (Auth.)

[en] NKS research work during the years 2002-2005 and its results have been evaluated against a set of criteria defined by the NKS Board. The evaluation encompassed the NKS-R (reactor safety) and NKS-B (emergency preparedness) programs and was conducted by two persons per program. The mode of work of the two evaluation teams was adapted to the special conditions of the program at hand, one being aimed more at the nuclear industry and the other at a more academic surrounding; in both cases, however, with great involvement of relevant national authorities. The findings of the evaluators are presented in this report. Financing and participating organizations, end users, deliverables, quality aspects, cost-benefit issues, time schedules, budgets and related issues are discussed. Finally, the sections on NKS-R and NKS-B, respectively, include conclusions and recommendations for future NKS work. (au)