[Study of the induction mechanism in Syrian hamster cells transformed by SV40 virus. I. Properties of a clonal cell line].
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Biomedical subjects
Publications and source records attributed to J Coppey.
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We investigate here, in A549 cells, the influence of a single short (1h) or long (24h) adriamycin (ADR) contact time on the long-term cytotoxicity of the drug and on the emergence of resistant cells. In contrast to a 1 h ADR contact, a 24 h treatment provokes the emergence of resistant cells overexpressing the Gp170 protein and this overexpression is maintained for at least three months without any drug selection pressure.
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The cytostatic efficiency of gamma-rays was determined following irradiation at 23 degrees C or 37 degrees C on A549 human lung carcinoma cells, irradiated either in monolayers or in three-dimensional organotypic cultures (nodules) with a dose-rate of 0.5 Gy/min. For the monolayers, the residual colony forming ability of single cells, and for the nodules, the growth rate, the proportion of regenerating or disaggregating nodules and the growth rate of regenerated nodules were measured. The efficiency of radiation was slightly improved by irradiating the monolayers at 23 degrees C compared to 37 degrees C. The difference was much more pronounced in the nodules, as deduced from (i) length of the time interval between irradiation and appearance of regeneration buds; (ii) growth rate of the regenerated nodules and (iii) growth rate of their progeny analysed over one year of subcultivation. Since organotypic cultures have a structure close to that of tumoral tissue, this result may present some useful applications for tumor radiotherapy.
64Cu was injected in the form of CuCl2 either by subcutaneous or by intraperitoneal route, and its distribution inside different organs was analyzed in 5 different tumor models, 4 in mice and 1 in rats. In all organs tested (blood, liver, kidneys, spleen, intestine, muscle, and tumor) no significant differences were observed in the results obtained after either injection route. All tumors analyzed (Krebs ascite, intestinal Leiomyo sarcoma, human tumor, mammary adenocarcinoma, either spontaneous or chemically induced) contained a relatively high concentration of 64Cu. For all tumor models tested, the 64Cu distribution was altered as compared with that of the corresponding control animals.
Inasmuch as misonidazole is a drug used in clinical trials for sensitizing radioresistant hypoxic cells in solid tumors, it seemed of interest to study its effects in human tumor cells maintained in tridimensional organotypic cultures. This type of culture involves: spatial organisation of the cells with fairly undisturbed differentiation patterns, minimal traumatizing culture conditions, and offers the possibility to follow post-treatment growth patterns over several months without disturbing the cultures. Misonidazole exhibited a radiosensitizing effect on irradiated nodules derived from a lung adenocarcinoma, and on cells of this tumor growing in monolayers. However, after a 4 hour contact with misonidazole at concentrations corresponding to the range of those found in the serum of treated patients, a significant stimulation of nodule growth was repeatedly observed, together with a strong increase in the frequency of sister chromatid exchanges. Similarly, after treatment of the same tumor cells in confluent monolayers, their colony forming ability was increased. These observations may account for some of the non- convincing therapeutic results obtained in clinical trials.
Residual colony forming ability (CFA) of cells from a human alveolar carcinoma (A549) was determined after 48 hours of contact with bleomycin (BLM) or cisdichlorodiammineplatinum (II) (DDP) using feeder cells arising from parallel cultures left in contact with sublethal BLM or DDP concentrations. The CFA of untreated cells was 60 to 80% (45% with X-irradiated feeder cells). Growing cultures were more resistant to DDP and more sensitive to BLM than plateau phase cultures. Subclones arising from a first treatment were resistant to a second BLM or X-ray treatment, but more sensitive to a second DDP treatment.