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Biomedical subjects

C Streffer

Publications and source records attributed to C Streffer.

At least 181 records · Page 10Linked to original sources

[DNA measurements and prognosis of rectal cancer].

The DNA concentration of 104 rectum carcinoma biopsies was measured by impulse cytophotometry. About 45% of these tumors had diploid cell lines. The rest contained hyperploid cell lines, and these patients had a less favorable prognosis than patients with diploid tumors. Metastasizing diploid as well as hyperploid tumors showed often a higher concentration of S-phase cells than the average of all patients. Tumor cell lines assessed in metastases had in general the same DNA concentration as primary tumors. The rate of cells with micronuclei increased with the concentration of S-phase cells found in the tumors. In surviving patients, the ratio S-phase cells - cells with micronuclei was often higher than in patients who died.

DNA, Neoplasm↗

Supraadditive formation of micronuclei in preimplantation mouse embryos in vitro after combined treatment with X-rays and caffeine.

The influence of caffeine (0.1 or 2 mM), X-rays (0.24 Gy [= 25 R] or 0.94 Gy [= 100 R]), or of a combination of both on the formation of micronuclei in early stages of preimplantation mouse embryos in vitro was studied. X-rays as well as caffeine induced micronuclei. The dose-effect curve after irradiation was linear for the dose range measured (0-3.76 Gy; = 0-400 R). Caffeine did not induce micronuclei if the concentration was 1 mM or less; between 1 mM and 7 mM, however, there was a linear increase in the number of micronuclei. A considerable enhancement of the number of radiation-induced micronuclei was observed when irradiation of the embryos was followed by a treatment with caffeine. Not only was the sum of the single effects exceeded by the combination effects, but the combination results even lay in the range of supraadditivity of the envelope of additivity.

Animals↗

Enhancement of radiation effects by mercury in preimplantation mouse embryos in vitro.

Mercuric chloride (3 microM or 10 microM) increased several effects of ionizing radiation (1 Gy) on preimplantation mouse embryos in vitro. Blastocyst formation, hatching of blastocysts, and the number of cells per embryo were affected by this increase in radiation risk. The formation of micronuclei, however, was not influenced either in experiments using mercury alone or in combination experiments with X-rays. Not only was the sum of the single effects exceeded in some of the combination experiments, but the dose-pairs, which were necessary for obtaining a certain effect, clearly fell to the left of the envelope of additivity. That is, the enhancement of effects cannot be explained merely by the shape of the dose-response curves, but there is an interaction between mercury and ionizing radiation.

Animals↗

Estimation of absorbed dose in cell nuclei due to DNA-bound 3H.

The average absorbed dose due to DNA-bound 3H in a cell nucleus was estimated by a Monte Carlo simulation for a model nucleus which was assumed to be spheroidal. The shape of the cell nucleus was found to be of minor importance in determining the average absorbed dose. The volume of the cell nucleus was the major dose-determining factor for cell nuclei which have the same DNA content and the same specific activity of DNA. This result was applied to estimating the accumulated dose in the cell nuclei of organs of young mice born from mother mice which ingested 3H-thymidine with drinking water during pregnancy. The values of dose-modifying factors for the accumulated dose due to DNA-bound 3H compared to the dose due to an assumed homogenous distribution of 3H in organ were found to be between about 2 and 6 for the various organs.

Animals↗

Distribution of micronuclei among single cells of pre-implantation mouse embryos after X-irradiation in vitro.

The frequency of micronuclei within single cells of pre-implantation mouse embryos in vitro was determined after X-irradiation. The embryos were irradiated in the late G2 phase of the two-cell stage (32 h p.c.) with doses between 0.5 and 14 Gy. The micronuclei were counted 48 h p.c. (with most of the control embryos in the four-cell stage) and 55 h p.c. (with most of the control embryos in the eight-cell stage). The distribution of micronuclei among the single cells of the embryos does not follow a Poisson distribution, but shows a clear tendency to over-dispersion.

Animals↗

The effects of radiosensitizers on intermediary metabolism in vivo.

In the liver, MISO has little effect on glycolytic intermediates but both the lactate and G3P contents are significantly decreased shortly after administration, whereas the level of ketone-bodies is raised. The changes in hepatic metabolite levels following treatment with SR-2508 are less marked. However, in an adenocarcinoma, both the lactate and ketone-body concentrations are enhanced with MISO. The redox equilibria states are shifted to the oxidized metabolites in the liver but instead to the reduced metabolites in tumor. These effects may have relevance for the radiotherapy in tumors.

3-Hydroxybutyric Acid↗

The influence of G2 progression on X-ray sensitivity of two-cell mouse embryos.

Naturally synchronous, two-cell mouse embryos were X-irradiated in vitro. In experiment 1, irradiation was either in the early or in the late G2 phase, which lasts about 14 hours. In experiment 2, irradiation of all the embryos was in late G2 but embryos with different intervals between irradiation and the first mitosis after irradiation were separated and investigated independently. After 2 Gy the time interval between irradiation in late G2 and the first mitosis post-irradiation was on the average about 9 hours; after irradiation in the early G2 phase about 13.5 hours. Development (hatching of blastocysts) and cell proliferation (cell number per embryo at the stage of the hatched blastocyst) was most impaired and the frequency of micronuclei (determined in four- or eight-cell embryos) was highest in the case of a short interval between irradiation in G2 and the first mitosis post-irradiation. It is concluded that a longer interval allows a longer period of DNA repair. The results also demonstrate a positive correlation between the extent of chromosomal damage (micronuclei) and the extent of cell death as well as the impairment of the development of the whole biological system.

Animals↗

Radiotherapy of soft tissue sarcomas with neutrons or a neutron boost.

A cooperative trial of neutron therapy for soft tissue sarcomas was started in 1978. 112 unselected and not previously irradiated patients (62% T3 tumours, 35% recurrent tumours) were treated up to June 1982 with neutrons alone. An analysis of these cases with a mean follow-up period of 22 months (range 12 to 45 months) is given in this report. Very preliminary results are presented for 60 patients treated with a neutron boost only. These showed a substantially lower complication rate. The major results of this phase II trial are: The survival rate of 3.5 years was strongly dependent on the stage of the tumour; for 8 patients with T1 tumours it was 100%, for 35 patients with T2 tumours, 77%, and for 69 patients with T3 tumours, 45%. The survival rate at 3.5 years was strongly dependent on surgery before the beginning of radiotherapy; for 54 patients after surgery without clinical evidence of residual tumour it was 73%, for 58 patients with inoperable primary or recurrent tumour, 47%. The survival rate of 31 patients with recurrence after neutron therapy was only 36%. The overall rate of serious complications was 28.6% after neutron therapy, but only 5% after neutron boost therapy (mean follow-up period: 12 months, range 5 to 48 months).

Follow-Up Studies↗

The effects of X irradiation, hyperthermia, and combined modality treatment on poly(ADPR)synthetase activity in human melanoma cells.

The effects of X irradiation and/or hyperthermia on both the intrinsic and total poly(ADPR)synthetase activity in permeabilized human melanoma cells were determined. All treatments were given in the early phase of exponential growth (early log phase). The intrinsic and total enzyme activities were significantly decreased immediately after heat treatment at either 42 degrees or 44 degrees C for 3 hr. These activities remained below the respective control levels over the whole period of culture, and some recovery was observed after 48 hr in both cases. X-ray doses of 3.76 to 11.28 Gy produced an increase in intrinsic activity 30 min postradiation (p.r.) but had no significant effect on the total activity. The increase may thus be associated with DNA repair. At later times after irradiation with 3.76 Gy no significant changes were observed. Combined treatment of X irradiation (3.76 Gy) followed by hyperthermia (42 degrees C for 3 hr) produced an enhanced decrease in intrinsic activity, equivalent to that after hyperthermia at 44 degrees C. The effects on cell proliferation were similar in both cases. However, the total activity was not modified to the same extent after combined treatment. The long-term decrease in total activity at 42 degrees C hyperthermia may be due to inhibitors produced during heat treatment since the enzyme activity was partially restored by changes of fresh medium. These results suggest that heat, X irradiation, and combined treatment act in a different manner on the chromatin-associated enzyme or at different sites on the enzyme complex.

Cell Division↗

N-methylnicotinamide as a possible prognostic indicator of recovery from leukaemia in patients treated with total-body irradiation and bone marrow transplants.

N-methylnicotinamide was determined in urine from patients with acute myelocytic leukaemia following total-body X-irradiation with 8.6 Gy and bone marrow transplantation. Patients that are alive and in excellent condition i.e. with acute leukaemia in full remission showed a distinct enhanced excretion of this metabolite about 20 days p.r. which returned to normal levels at about day 40 p.r. Patients that have died intercurrently of early leukaemic recurrences showed considerable fluctuations in N-methylnicotinamide excretion over the entire period and no "normalization" of levels in these patients was seen. In those cases where late leukaemic recurrence or infections were the cause of death, usually after discharge from the clinic, excretion patterns typical of those seen in disease-free patients were observed. We thus conclude that this metabolite appears to be a suitable tentative prognostic indicator for the overall state of recovery from leukaemia in the patients.

Adult↗

[Studies in the small intestine of mice after fractionated neutron and x-ray irradiation].

Several groups of mice received a whole-body irradiation with X-rays and neutrons. The survival and the number of crypts per intestinal circumference was measured after one-time, two-time, three-time, and four-time fractionation. The irradiation interval was 24 hours. Survival rate and number of crypts were compared to one another. There were discrepancies which could be explained by determining the right moments of examination. Thus it seems not recommendable to use the system of small intestine crypts for experiences with fractionated irradiations. The RBE values increased with the rising number of fractions. If Dn-Dl values were calculated, they increased on the one hand with the rising fractionation, on the other hand with the rising total dose. This effect was more marked after X-ray irradiation, less after neutron irradiation. This may be explained by the fact that, contrary to neutron irradiation, the recovery following to sublethal lesion by X-rays had not been exhausted.

Animals↗

An approach to the individualization of cancer therapy--determination of DNA, SH-groups and micronuclei.

Localization and histo-pathology are the basis for the decision, which modality of therapy is used to treat a tumour today. The great variety of biological factors in human tumours is generally largely neglected. The variety of such factors is shown by measuring the DNA content in tumour cell lines, their distribution in the cell generation cycle and the content of bound SH-groups in the cell nuclei. Further the micronuclei which are an expression of cytogenetic damage and which can be used as an indicator of cell loss have been determined. These parameters have been studied in primary and secondary tumours in the brain as well as in rectal adenocarcinoma. It was found that primary brain-tumours had only diploid and tetraploid cell lines while in almost 50 per cent of metastases in the brain and of the rectum adenocarcinoma aneuploid cell lines appeared. These latter cell populations had a higher number of cells in S-phase. The cells in the primary brain-tumours had less micronuclei and appeared as comparatively stable cell lines. Also a difference in the content of nuclear SH-groups could be demonstrated between primary brain-tumours and brain-metastases. In one recurrent tumour, which could be compared with the original tumour, the amount of bound nuclear SH-groups increased by a factor of about 15. In several cases biopsies from adenocarcinoma of the rectum could be studied before and after preoperative radiotherapy. In aneuploid tumours the reduction of the tumour cell line could be demonstrated, at the same time the number of micronuclei increased. However this was not consistent in all investigated cases.

Adenocarcinoma↗

Effects of a combination of X-rays and caffeine on preimplantation mouse embryos in vitro.

The influence of a combination of caffeine (0.1 mM, 1 mM, or 2 mM) and X-rays (0.24 Gy, 0.94 Gy, or 1.88 Gy) on preimplantation mouse embryos in vitro was studied under different conditions. The agents were applied either singly or in combination. The embryos were irradiated in the G2-phase of the two-cell stage (28 h p. c. or 32 h p. c.) either 1 h after or immediately before application of caffeine. Caffeine was present during the whole incubation period (until 144 h p. c.). The effects on the microscopic visible development (formation of blastocysts 96 h p. c., hatching of blastocysts 144 h p. c.) and on the cell numbers of embryos at different times (48 h p. c., 56 h p. c., 96 h p. c., 144 h p. c.) were determined. We found conditions under which caffeine markedly enhanced radiation risk, i.e., under which the combination effect exceeded the sum of the single effects. This is true, in particular, for the embryonal development, for which the risk may almost be doubled, whereas the enhancement of risk is not so great for the proliferation of cells. In some cases the combination results lie even outside the envelope of additivity in the range of supra-additivity. The amount of caffeine necessary for such marked effects, however, is so high (at least 1 mM caffeine for rather long times), that it is almost impossible to reach them in vivo by consumption of caffeine-containing beverages.

Animals↗

The effects of lead and X-rays, alone or in combination, on blastocyst formation and cell kinetics of preimplantation mouse embryos in vitro.

Two-cell embryos in late G2-phase (cytofluorometrically determined) at 32 hours post-conception were treated in vitro with PbC12 (0 . 1 or 1 . 0 micrograms per ml). An additional group was X-irradiated 1 hour later (0 . 94 Gy) with or without lead treatment. Lead alone impaired formation and hatching of blastocysts. The combined treatment increased this deleterious effect on preimplantation development but synergism was not observed. Cell proliferation was disturbed by lead alone but to a higher degree by lead plus X-rays. A pronounced reduction of cell number per embryo was found during the period after reaching the morula stage although the labelling index increased. Apparently cell death occurred. Unlabelled S-phase cell nuclei (comparison between autoradiographic results and cytofluorometric DNA-determinations on the same isolated cell nuclei) and cell nuclei with a hyperploid (0 . 1 microgram PbC12 + 0 . 94 Gy) or hypoploid (1 . 0 microgram PcC12 + 0 . 94 Gy) DNA-content may have contributed to this cell loss. Labelling of cell nuclei which according to their DNA-content were not in S-phase was only observed when 0 . 1 microgram PbC12 alone or in combination with X-rays was used. This effect may be due to unscheduled DNA-repair synthesis or to the induction of chromosome aberrations (acentric fragments or non-disjunction).

Animals↗