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Biomedical subjects

C Streffer

Publications and source records attributed to C Streffer.

At least 199 records · Page 11Linked to original sources
PubMed1983

Tritium distribution in newborn mice after providing mother mice with drinking water containing tritiated thymidine.

Throughout gestation pregnant mice received drinking water which contained [methyl-3H]thymidine (18.5 kBq/ml). The newborn mice were divided into two groups. One group was nursed by their own mothers, which were further supplied with tritiated thymidine until 4 weeks after delivery (Experiment I). The other group was nursed by "nonradioactive mothers" which were given no tritiated thymidine (Experiment II). Tritium incorporation into the small molecular components of the acid-soluble fraction, lipid, RNA, DNA, and protein was analyzed for the newborn mice at various ages. In Experiment II, total radioactivity per gram tissue decreased initially after birth with a half life of 2.5-2.9 days in spleen, liver, intestine, stomach, thymus, lung, kidney, heart, and brain. At about 2 weeks after birth, a slower component of tritium elimination due mainly to the DNA-bound tritium appeared. Specific activity of DNA at birth was organ specific, highest in heart and lowest in thymus. Cumulative absorbed dose in various organs was estimated for the first 4 weeks after birth based upon an assumption that total and DNA-bound tritium are uniformly distributed. The result showed that organ specificity of dose accumulation is obvious for DNA-bound tritium, highest in spleen (1.15 mGy) and lowest in brain (0.13 mGy). It was also shown that the tritium supply from mother's milk is of minor importance for dose accumulation of DNA-bound tritium in the cell nuclei of organs of suckling mice.

Animals↗
PubMed1983

A comparison of the cell kinetics of pre-implantation mouse embryos from two different mouse strains.

The progression of pre-implantation mouse embryos through the first, second and third embryonic cell cycle was investigated cytofluorometrically. In contrast to most of the previous studies, the ova were spontaneously ovulated and the mating period of the ova donors was short (06.00-09.00 hours). The embryonic cells proceeded through the first, second and third cell cycle as a cohort. Thus it was possible to estimate the duration of the cell cycle phases directly from the DNA histograms. The length of the cell cycle phases differed between the embryos of the two different mouse strains. The most pronounced differences were found for the G2 + M phases (first cell cycle: 8 hr for Strain I and 5 hr for Strain II; second cell cycle: 11.5 hr and 14 hr respectively). However, in accordance with previous investigations, common features of the early pre-implantation cell kinetics were also observed: increasing length of the S phases from the first to the second cell cycle and very short G1 phases in the second and third cell cycle. The cell proliferation of the embryos of both strains after the third cell cycle was characterized by exponential growth. The proliferation rate was higher in Strain I embryos than in Strain II embryos (steeper increase of the growth curve). At the end of the pre-implantation development (hatched blastocysts), the growth curves of both strains decreased. The differences concerning the durations of the cell cycle phases and the proliferation rates are considered to be strain specific. It is suggested that the differences in the pre-implantation cell kinetics which have been described generally reflect the strain specificities more than different investigational methods and/or different grades of synchrony of early pre-implantation embryos.

Animals↗
PubMed1982

Combined treatment of preimplantation mouse embryos in vitro with sodium nitrite and x-rays.

Man takes up nitrite in a considerable amount. Effects of nitrite on DNA have been reported; therefore, interaction between nitrite and radiation might be possible. Preimplantation mouse embryos in vitro were treated with a combination of sodium nitrite (1 mM or 2.5 mM) and X-rays (0.94 Gy) in order to obtain some information whether radiation risk is influenced by the presence of nitrite. The microscopic visible development up to 144 h post conceptionem (h p.c.), the number of cell nuclei, and the number of micronuclei were determined. None of the experimental results gives any indication that radiation risk is influenced by nitrite. All effects after combined treatment correspond to the sum of the single effects.

Animals↗
PubMed1982

[Proliferation kinetics of PHA-stimulated lymphocytes after whole-body irradiation of patients with non-Hodgkin lymphomas (author's transl)].

A number of patients suffering from non-Hodgkin lymphomas received a whole-body irradiation with 15 rad per fraction (10 fractions). Before and after every second fraction, the proliferation kinetics of the peripheral lymphocytes was examined after PHA stimulation (DNA content per culture as cell number equivalent, incorporation of thymidine into DNA after isolation of DNA, distribution of cells within the cell cycle). After a total dose of 60 rad, the lymphocytes of nine among twenty patients showed a decrease of all proliferation-kinetic parameters. This decrease was followed by an increase up to values lying partly above the initial values. A second group did not show this increase. No correlations could be found between these changes and the clinical course or the symptomatology. The formation of micronuclei in lymphocytes of six patients could be examined before the whole-body irradiation and after an in-vitro irradiation. The results suggest the possibility of an individual determination of the radiosensibility of non-Hodgkin lymphomas.

Adult↗
PubMed1982

[Irradiation of mouse embryos in pronucleus and 2-cell stages: dependence of micronucleus formation and cell proliferation upon DNA amount and cell cycle phase].

1-or 2-cell mouse embryos were X-irradiated with 1.88 Gy. At irradiation time both pronuclei of each 1-cell embryo (see introduction) had a haploid DNA-amount and were in G1-phase. In contrast the cell nuclei of the 2-cell embryos had a tetraploid DNA-amount and were in late G2. DNA-amount and the cell cycle phases respectively were determined cytofluorometrically. The blastocyst formation was more impaired after irradiation of 1-cell embryos (28%) than 2-cell embryos (73%; controls: 100%). Cell death, which was observed in the cell proliferation investigations, should be the most important reason for the impaired early embryonic development. The different extent of cell death can be explained with the different amount of micronucleus formation. This chromosomal damage, which leads to a hypoploid DNA-amount of the cell nuclei, was more bulky after irradiation of 1-cell embryos than 2-cell embryos. Mechanisms which could cause a higher micronucleus formation after irradiation of haploid cell nuclei (pronuclei) in G1-phase than after irradiation of tetraploid cell nuclei in G2-phase are discussed.

Animals↗
PubMed1982

Aspects of biochemical effects by hyperthermia.

Hyperthermia caused an immediate decrease of DNA, RNA, and protein synthesis. The latter process was most sensitive. Initiation of DNA synthesis at the transition from G1-to S-phase and at the start of new replication units were inhibited. These effects were responsible for the growth delay of cells and were potentiated with irradiation. The immediate inhibition of protein synthesis was due mainly to a disaggregation of the synthesizing mechanisms. It led to a decrease of enzyme activities with a short biological half-life, e.g., ornithine decarboxylase. Lysosomal hydrolytic activities might be enhanced after hyperthermia and contribute to tissue damage. During hyperthermia, glycogen breakdown and glucose turnover through glycolysis and the citrate cycle were apparently increased, but after hyperthermia, respiration and glycolysis were reduced. No lactate accumulation occurred, but other acidic metabolites were enhanced and could induce a metabolic acidosis hours later. A glucose load potentiated the effects on respiration and glycolysis. Immediately after hyperthermia, a lactate accumulation was observed under these conditions. A formula is given by which the ratios of reduced to oxidized substrates might indicate the redox state in different cellular compartments, with oxygen pressure, and during other metabolic conditions. Such changes of the intracellular milieu are important for the thermosensitivity of cells.

Animals↗
PubMed1982

[Influence of actinomycin D or ethidium bromide on the radiation risk in embryos of mice in the preimplantation stage in vitro].

The authors examined if the radiation risk (after X = irradiation with 0.94 Gy or 3H-thymidine treatment with 0.5 kBq/ml) in embryos of mice of the preimplantation stage in vitro is increased by the presence of actinomycin D (0.3 nM for 112 hours or 100 nM for 90 minutes) or ethidium bromide (0.5 microM for 112 hours). The influence of these substances on the radiation effect was determined by microscopic observation of the development of embryos and by investigation of the cell proliferation. The radiation risk was regarded to be increased if the combined effect was significantly higher than the total amount of the individual effects. The radiation risk for the morphologic development of the embryos was significantly increased by actinomycin D; the combined effects were about 1.3 times higher than the total amount of the individual effects. There was no increased risk for the cell proliferation. Ethidium bromide did not modify the radiation risk neither with respect to the morphologic development nor regarding the cell proliferation.

Animals↗
PubMed1981

Effects of a combined treatment with X-rays and phenols on preimplantation mouse embryos in vitro.

Phenols are found everywhere in the environment. Therefore, the investigation of possible interaction between phenols and radiation is of some interest. The effects of a combination of X-rays and phenols (phenol itself and p-nitrophenol) were measured by the preimplantation mouse embryo-system in vitro. The microscopic visible development up to 144 h post conceptionem (h.p.c.), the number of cell nuclei, the DNA-content of each nucleus, the mitotic index, the labelling index, and the number of micronuclei were determined. There was not any indication that the effect of the irradiation was enhanced in a synergistic manner by the presence of phenols. All parameters measured lead to the conclusion that the effects of phenols plus X-rays are, at most, additive.

Animals↗
PubMed1981

Micronucleus formation in preimplanted mouse embryos cultured in vitro after irradiation with x-rays and neutrons.

Preimplanted mouse embryos cultured in vitro were irradiated with X-rays and neutrons in the late G2-phase of the 2-cell stage. Both radiation qualities induced micronuclei at very low doses. The kinetics of micronucleus formation during the first and second cell cycles after X-irradiation depended on the radiation dose and on the extent of the division delay. New micronuclei appeared to be formed even after the third and later post-irradiation mitoses. The shape of the various dose-effect curves and the mechanism of micronucleus formation by the two radiation qualities are discussed.

Animals↗
PubMed1981

Misonidazole as a radiosensitizer in the radiotherapy of glioblastomas and oesophageal cancer. Pharmacokinetic and clinical studies.

Since May 1978 the hypoxic-cell radiosensitizer, misonidazole (MIS), has been under clinical investigation in a phase III trial with multiple doses of the drug in 11 patients with brain tumours (seven glioblastomas, four recurrent brain tumours) and three patients with oesophageal carcinoma. The doses of MIS administered were usually well tolerated but the principal toxicities observed were peripheral neuropathy as well as nausea and vomiting was completely reversible. The incidence of neuropathy was not related to the pharmacological parameters of plasma level or half-life. Pharmacological assessment by high-pressure liquid chromatography included assays of plasma, urine and cerebrospinal fluid. The demethylated product, Ro-05-9963, was detected as the major metabolite. Peak plasma levels were obtained one to four hours after administration of MIS, with a half-life of five to ten hours. Cerebrospinal fluid levels of MIS correlated well with those of the plasma. MIS was mainly excreted as the demethylated metabolite, but less than 40% of the given dose could be recovered. The results obtained suggest that the present MIS dosage for glioblastoma patients results in a low plasma level with no observable therapeutic effect.

Adult↗
PubMed1981

[Micronucleus formation compared to the survival rate of human melanoma cells after X-ray and neutron irradiation and hyperthermia].

After neutron and X-ray irradiation and combined X-ray irradiation and hyperthermia (3 hours, 42 degrees C), the survival rate of human melanoma cells was measured by means of the colony formation test and compared to the formation of micronuclei. Neutrons had a stronger effect on the formation of micronuclei than the combination of X-rays and hyperthermia. X-rays had the lowest effect. The dose effect curve showed a break at that dose level at which a reduction of cells was observed in the cultures. A good relation between survival rate and formation of micronuclei was found for the X-ray irradiation, but not for the neutron irradiation and the combined treatment. These observations are discussed. At least for X-rays, the micronucleus test has turned out to be a good screening method for the radiosensitivity of a biologic system.

Cell Line↗
PubMed1980

Kinetics of cell proliferation in the pre-implanted mouse embryo in vivo and in vitro.

The cell proliferation of pre-implanted mouse embryos was investigated after development in vivo and in vitro. The studies were started at the pronuclear stage, 2 h post conception (p.c.) and continued until the hatching of blastocysts, 120-144 h p.c. The number of cell nuclei, the DNA content of each nucleus, the mitotic index and the labelling index were determined. From these data it was possible to calculate the length of the cell generation cycle and its various phases. With the exception of the first cell cycle the S-phase was constant. The G1- as well as the G2-phase varied in length during the different cell cycles. From 31-72 h p.c. the increase in cell number was exponential. After cultivation in vitro this increase was smaller than in vivo. At later periods the proliferation rate decreased with proceeding development. In late blastocysts most of the cells were in the G1-phase. The development of the embryos was somewhat faster in vivo than in vitro. But in principle conditions were comparable.

Animals↗