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H Fritz-Niggli

Publications and source records attributed to H Fritz-Niggli.

At least 37 records · Page 2Linked to original sources

Rutoside and the X-ray induced damage in jejunal mucosa of mouse.

The effect of O-(beta-hydroxyethyl)-Rutoside on the radiation response of mouse small intestine was investigated. The post-irradiation mitotic regeneration in jejunal crypts, the survival of crypt stem cells and the post-irradiation mortality of animals were taken as criteria. Multiple treatment with rutoside (300 mg/kg/injection) combined with a whole-body-X-irradiation failed to show protective effect in all the cases studied. Some possibilities which may explain these results are presented.

Animals↗

Cellular damage and recovery of the early developing mouse eye following low dose irradiation. II. X-rays on day 9 of gestation.

Mouse embryos on day 9 of gestation were exposed in utero to 90 rad X-rays. At different time intervals after treatment the eye primordia were examined for cell death. The irradiation caused an altered necrosis pattern compared with day 8, and massive cell killing during a limited time period. The rapid recovery from the pronounced damage points to a high restitution efficiency of the involved tissue.

Animals↗

Combined application of misonidazole and piotron pions on mouse embryos.

Mouse embryos on day 8 of gestation were irradiated with negative pions (12.5-100 rad) or 200 kV X-rays (12.5-150 rad). Misonidazole (MISO), a hypoxic cell radiosensitizer, was applied 30 min before exposure. On day 13 the fetuses were examined for lethality, growth retardation and malformation. No significant embryolethal effects were observed after irradiation alone in the dose range of 12.5-100 rad (X-rays or pions). However, MISO alone and in combination with radiation led to high rates of lethality. The frequency of growth retardation was significantly increased at 100 rad and in combined treatments at low radiation doses. MISO and irradiation with 50 rad and more induced complex damages consisting of multiple and severe malformations and growth retardation. The relative biological effectiveness (RBE) for teratogenic effects was 1.6. In conclusion, the combined application of MISO and radiation of different LET revealed a strong enhancing action compared to single treatments. The extent of enhancement depends on both radiation quality and dose.

Abnormalities, Drug-Induced↗

Response of mouse small intestine to fractionated doses of pions.

The effect of single or fractionated doses of stopping pions or 200 kV X-rays on the mouse jejunal crypt cells was used to determine in vivo RBE values. For single fraction, the pion/X-ray RBE was 1.27 and it increased to about 1.31 when two fractions were applied at 3 or 24 h interval. When four fractions were given at 3 h intervals, the RBE was 1.46. This is because the fraction of "dose repaired" was always higher for X-rays than for pions and this difference was enhanced when more dose fractions were used. The data presented is, in general, consistent with the biological effects of pions reported for other in vivo end points.

Animals↗

Oxygen-effect as an inhibition of repair: radiation studies on excision repair deficient mei-9L1-embryos of Drosophila.

The excision repair deficient mei-9L1-embryos of Drosophila melanogaster are up to four times more radiosensitive than normal +/+ embryos. The lack of oxygen-effect in the repair deficient 4-h-embryos and the reduced O2-effect in the 13/4-h embryos suggest an interpretation of the oxygen effect as a modification of the ability to repair. The conversion of the early death (heavy damage) to late death (slight damage) by irradiation of normal embryos in N2 supports this interpretation. This theory can also explain the dependence of O2-effect on LET. The spontaneous lethality and the increase in radiosensitivity depend in heterozygous mei-9L1-embryos strictly upon the genotype of the mother, thus representing a maternal effect.

Animals↗

[Reduction of radiation-induced early skin damage (mouse foot) by O-(beta-hydroxyethyl)-rutoside (author's transl)].

The effect of bioflavonoid, O-(beta-hydroxyethyl)-rutoside (HR) on early radiation-induced skin damage was examined, using the mouse foot system; the response to radiation is not species specific and comparison with the clinical situation is therefore possible. The aim was to see whether HR, which is highly effective in protecting against late damage, is also able to reduce early effects. Early reactions were considered to be erythema, swelling and ulceration and occurring up to 30 days after irradiation. It was found that HR significantly reduces early damage, both after a single dose and after fractionated irradiation with low doses. A single pre-treatment dose of HR and pre-treatment together with 30 days post-treatment administration were both found to be effective. The protective effect became more marked with increasing radiation dose (single irradiation). Reduction of late effects is produced optimally by an interval of 0.25 hours between application of HR and irradiation, and this is also true for early skin damage. The early effects are partly reversible, but there is possibly an interesting correlation between these and irreversible late effects (such as loss of toes); a similar mechanism, presumably affecting the vascular system, may therefore be postulated. The protective action of this well tolerated, highly effective substance, which apparently protects normal tissues from early and late injury, is discussed.

Animals↗

The suitability of negative pions for radiotherapy: 4 years preclinical research with the biomedical PiE3-beam at SIN.

The radiobiological experiences over 4 years research with the biomedical pion channel of the 590 MeV proton-accelerator of the Swiss Institute for Nuclear Research (SIN) have been summarized. Mainly sensitive biological systems have been chosen (limiting factor: dose-rate not more than 10 rad/min, exceptionally till 30 rad/min). The RBE values in the peak region vary between 0.7-3.3 and in the plateau region between 0.4-1. The gain factors for pion radiotherapy of cancer are, beside the excellent physical dose distribution, irradiation in the same treatment with two types of radiation: sparsely ionizing (low LET) radiation in plateau (healthy tissue) region and densely ionizing (high LET) radiation in peak (tumor) region. The biological effectiveness ratio in peak and plateau as the clinically most important relation vary between 1.4-4.2. This is valid also for clinically limiting factors such as reaction of skin, of small intestine, vascular damage, dominant lethals in hypoxic cells, tumor induction. For peak pions the RBE in hypoxic cells (tumor cells) can be much higher than in euoxic cells (healthy tissue). This preclinical work supports the hope in a highly effective cancer therapy with negative pions.

Animals↗

Effect of negative pions, relative to 140 kV -- 29 MeV photons and 20 MeV electrons, on proliferation of Ehrlich ascites carcinoma cells.

The effect of negative pions (peak and plateau), photons (140 kV and 29 MeV), and 20 MeV electrons on the proliferative capacity of Ehrlich ascites carcinoma cells was investigated. Proliferative survival curves plotted for the modalities employed are presented. Under the experimental conditions used, the peak pions were more effective than plateau pions by a factor of about 1.4. For 50% survival, 140 kV X-rays had the same effect as peak pions but the latter was more effective (factor 1.2) at 10% survival level. When 140 kV X-rays were taken as the standard, following are the RBE values calculated as 50% survival level: plateau pions --0.73; peak pions --about 1.0; 29 MeV photons --0.73 and 20 MeV electrons --0.6. The results obtained are compared with those reported on other tumor systems and biological test objects.

Animals↗

Cell survival over the depth profile after irradiation with a negative pion beam.

The colony-forming ability of Chinese hamster fibroblast cells in vitro has been investigated throughout the depth dose profile of a negative pion beam. In the peak and 2 cm beyond, the RBE for macroclones (more than 50 cells per clone) was 1.3 and in the plateau region 0.8--1.0. All of the microclones (2-49 cells per clone) were observed as well. The RBE values are the same for peak and somewhat higher for plateau and post peak than found in cell survival studies referring to macroclones.

Animals↗

Chromatid breaks induced in Chinese hamster cells by low doses (12--100 rad) of pi--mesons.

Monolayer cultures of the fibroblast-like Chinese hamster cell-line 19/1 were irradiated in the G2-phase of the cell cycle by pi--mesons (6 rad/min peak-pion dose rate). Frequencies of induced single- and isochromatid breaks, acentric fragments and interchanges were compared with data obtained from 140 kV X-rays. The RBE-values were for the pion dose peak between 0.8--1.2 and for the pion dose plateau 0.5--0.9. Whereas for single chromatid breaks there was no significant difference between X-rays and peak pions for identical physical doses, the isochromatid breaks alone showed a significantly higher frequency for 100 rad peak pions.

Animals↗

Preclinical radiobiology with pions: RBE--values for mouse skin damage as a function of single doses of pions.

The macroscopic reaction of the mouse skin was used to derive RBE values for negative pi-Mesons. Hind limbs of mice were irradiated with pions or X-rays. The pions were produced by the 590 MeV accelerator of the Schweizerisches Institut für Nuklearforschung (SIN). Early reaction was assessed over a period of 6--30 days after irradiation with single doses (20--45 Gy). The radiation damage was scored using an arbitrary scale of effect. The time pattern of development of the skin reaction and the subsequent healing after exposure both to pions and X-rays were similar, indicating that depletion and repopulation of the basal cells of the skin were comparable, both after pions and X-rays. RBE values as a function of pion doses at the peak (dose maximum), plateau and at the postpeak (12 mm downstream of the dose maximum) were computed with nonparametric statistical methods. The RBE at the peak and at the plateau relative to X-rays of the same dose rate was 1.15--1.25 and 0.85, respectively. The RBE of peak pions manifested a marked dependence on dose, when plateau pions were chosen as reference radiation. In this experiment there was no significant difference in RBE between peak and postpeak. The importance of some experimental condition (dose rate, irradiation volume) is discussed.

Animals↗

Low-dose effects of X-rays and negative pions on the pronuclear zygote stage of mouse embryos.

Mouse embryos in the pronuclear-zygote stage (day 0 of gestation) were irradiated with 13.5 rad of 140kV X-rays or negative pions. On day 13 the fetuses were examined for developmental anomalies such as intrauterine death, growth retardation and malformations. Significant decreases in the percentage of normal implantations were obtained with peak pions (high LET) and X-rays, whereas the effect of plateau pions was less obvious. Irradiation with peak pions was more effective than with X-rays by a factor of about 1.7.

Abnormalities, Radiation-Induced↗

Effect of negative pi mesons on vascular permeability of brain in neonatal rats.

Neonatal rats and their radiation-induced cerebral petechial hemorrhages were used as an experimental system for evaluating the effects of negative pions on healthy tissue and especially on the microvasculature. Dose response curves for peak and plateau pions (dose range 150--250 rad and 100--400 rad, respectively) were obtained and compared with those of 200 kV X-rays of corresponding dose rates. The RBE of the peak pions was 1.1, that of the plateau pions 0.6 resulting in a peak/plateau ratio of 1.8. Implications were made as to the importance of this favorable peak/plateau relationship since the response of the capillary endothelium to pion-irradiation might be one of the limiting factors in radiotherapy.

Animals↗