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Biomedical subjects

H Fritz-Niggli

Publications and source records attributed to H Fritz-Niggli.

At least 19 recordsLinked to original sources

100 years of radiobiology: implications for biomedicine and future perspectives.

The development of radiobiology from the very early detection of the biological action of X-rays to the knowledge of today is described in sections on radiation chemistry and biochemistry, mutation and cancer induction, and embryonic damage, as well as the dependence of radiation response on radiation quality and temporal dose distribution (repair) and the interaction with other factors. For medicine radiobiology serves as a basis for radiotherapy and radiological protection. The effect of very low doses, and their possible biopositive effect (hormesis and adaptive response), is also discussed, as are the health hazard of radon, health risks after the Chernobyl accident, and space radiobiology. The radiobiology of the future will be concerned with biomolecular and genetic implications, problems of damage and repair, and connected problems like hormesis.

Animals↗

Adaptive response to dominant lethality of mature (class A) and immature (class B) oocytes of D. melanogaster to low doses of ionizing radiation: effects in repair-proficient (yw) and repair-deficient strains (mei 41D5 and mus 302D1).

Mature oocytes (class A) and immature oocytes (class B) from a repair-proficient yw strain and two repair-deficient strains (mus 302D1 and mei 41D5) were initially X-irradiated with 0.02 Gy and subsequently treated at various time intervals with 2 Gy. They were tested for dominant lethality (early and late death). For each strain and stage the observed values were below those expected on the basis of additivity of the effects of the two irradiations given separately. These results indicate the existence of a repair-stimulating effect of low doses for the repair-deficient strains as well as for the highly radiosensitive mature oocytes. This 'adaptive response' was highest for mei 41, lower for yw and lowest for mus 302, and also involved 'late death' lethality (real dominant mutations). The finding that the two repair-deficient strains showed significant differences in normal dominant lethality, as well as in radiosensitivity and adaptive response, is consistent with dissimilarities in the repair defect.

Adaptation, Physiological↗

Experimental study on the fractionation schedule for proton irradiation of uveal melanoma.

Greene melanoma in the anterior chamber of rabbits was irradiated by protons to find the isoeffect curve for proton irradiation fractionated into one, two, three or four doses. The isoeffect curve for tumor tissue remained constant between one- and three-dose fractionations and rose with four-dose fractionation. The isoeffect curve for normal tissue approximately followed the Ellis equation. Therefore, the optimal irradiation schedule should be in the range of three fractions because this best spares normal tissue while delivering a tumoricidal dose to the lesion. The relative reduction of the total dose from four- to one-dose fractions of intraoperative irradiation should be 20%.

Animals↗

Response of murine small intestine to combined treatment with fostriecin and X rays.

This radiobiological investigation was based on the measurements of crypt cell survival in mouse small intestine when the animals were injected with a single dose of fostriecin or streptomycin, and subsequently irradiated to the whole body with graded doses of X rays. The experimental data obtained indicated that fostriecin decreased the isoeffect dose to murine intestine by a factor of 2.3, whereas streptomycin did not influence the radiation response. The biological effects of fostriecin on various tumour cell systems in vitro and in vivo are briefly reviewed. The possible basic mechanisms involved in the radiosensitizing action of fostriecin and the implications of these results in the radiation protection of normal tissues are discussed.

Alkenes↗

Modifying factors on repair phenomena.

Every step of radiation damage repair can be modified by several factors like temporal and local energy distribution (LET), physiological conditions, biochemical and chemical composition of the target environment. Most interesting in the case of space radiation is the possible influence of high LET and of microgravity which could change the repair i.e. fusion capacity as well as the phenomenon of self assembly.

Animals↗

Calcium-binding parvalbumin in Drosophila testis in connection with in vivo irradiation.

Assuming a possible role of calcium in the function of the germinal proliferation centre in the testis of Drosophila melanogaster, the distribution of Ca2+-binding protein parvalbumin and structural related proteins in male gonads was tested by several biochemical and immunohistochemical methods. The two dimensional PAGE analysis on 3000 gonads of pupal stages suggests the presence of parvalbumin in this tissue. Immunohistochemical studies confirmed this finding. Parvalbumin-immunoreactivity was located in (or near) membraneous systems, like mitochondria and (or) microtubuli. The immunohistochemical analysis of irradiated gonads showed no radiation damage effect on the distribution of parvalbumin in certain cells and cell components.

Animals↗

Qualitatively different induction of germ cell mutations by heavy ions. A dual target theory.

The problem of the dependence of the biological efficiency of ionizing radiation on the Linear Energy Transfer (LET) is still unsolved. Unexpected reactions of heavy ion irradiated cellular systems such as an increasing Relative Biological Effectiveness (RBE) up to a LET of about 100 keV/micron and then a decrease below 1 oblige to dismiss some conventional interpretations. Several years ago we suggested that, especially by higher ionization density in addition to the DNA, repair systems and (or) membraneous systems could also be injured (dual target theory). Our experiments with heavy ions at the Lawrence Berkeley Laboratory with LET's between 102-970 keV/micron on different types of mutations show a strict distinction between events connected with fusion modalities (repair or misrepair) and those associated with nonfusion. With very high LET misrepair reactions such as translocations disappear, suggesting the direct damage of the repair systems and confirming our previous experiments with peak pions and ions of LET's between 1100-4800 keV/micron.

Animals↗

Alterations in the length of jejunal villi in mice irradiated with graded doses of X rays.

The length of villi protruding into the jejunal lumen influences the absorptive surface involved in digestion. Since it is an important functional end-point, a correlation between the X-ray dose applied and the average length of jejunal villi was investigated, with the possibility of using it as a radiobiological test system. Mice were given whole-body irradiation in the low- (4-7 Gy) or high-dose (9-12 Gy) range in a single fraction. Villus length was measured in arbitrary units from stained histological sections. It was found that villus length was affected by both the dose ranges used, but the effect observed in the low-dose range was not dose-related, whereas in the high-dose range there was a correlation between the radiation dose applied and the reduction in the average length of villi. Therefore, it is not suitable as an assay for low doses and for high doses there is already a test system (the microcolony survival assay) which is more practical and widely used. Factors which may influence villus length as well as the basic mechanisms involved are reviewed briefly. Experimental data presented indicate that the villus length may also be dependent on the number of crypts per jejunal circumference.

Animals↗

[Clinical radiation biology].

Clinical radiobiology covers three fields. 1. Radiation hazards and radiation protection: The fundamentals for evaluation of radiation hazards in man are reviewed. The biomedical effect of low doses is of chief importance in regard to use of radiation in radiodiagnosis and medicine, which account for most artificial radiation exposure in man. Interesting features are stochastic effects without a threshold dose, such as induction of cancer, mutation and developmental anomalies. 2. Optimization of radiotherapy: Apart from amelioration of temporal radiation distribution, possible modifiers are tested such as chemical substances (as sensitizers of tumor cells and protectors of healthy tissue) or hyperthermia. For selective irradiation of the tumor, various kinds of radiation are evaluated, e.g. pions, protons and heavy ions. 3. Public education and information.

Health Education↗

Antiteratogenic and anticarcinogenic effects of X-rays in urethane-treated NMRI mice.

A single intraperitoneal injection of urethane (ethyl carbamate) induces lung tumours in 80 per cent of male and 100 per cent of female NMRI mice, respectively. In the course of time the initially benign adenomatous tumours can develop into malignant adenomatosis of the lung (alveolar cell carcinoma). For an analysis of the mechanisms of tumour development and the possible interactions involved, low doses of X-rays (5-100 cGy) were administered 6 hours after urethane treatment. A significant anticarcinogenic and, also, anti-teratogenic action was observed. This implies that in both cases similar mechanisms are involved. Single injections of vitamin C or chloroquine counteract the urethane effects in the same manner as do the low doses of X-rays, but probably by different mechanisms.

Abnormalities, Drug-Induced↗

Synergistic interaction between vindesine and X-rays in the prenatal development of mice.

The modification of radiation damage by various concentrations of the oncolytic drug vindesine was studied macroscopically, using mouse embryos during the early organogenesis (days eight and nine of gestation) as the test system. The analysis at term showed that the developmental toxicity of vindesine depends on the dosage and the time of administration. In the lower dose-range (0.25 and 0.35 mg/kg), the only reaction was growth retardation, whereas higher concentrations (0.5 and 1.0 mg/kg) led mainly to an early resorption of implants. The more differentiated stage (day nine) exhibited a much higher sensitivity to vindesine than the embryo on day eight. Conversely, the harmful action of 0.9 Gy X-rays was restricted to the earlier period of organogenesis. The incidence of abnormalities after irradiation on day eight was 4.5 times higher than the one following exposure on day nine. The combined exposures showed a radiosensitizing capacity of the drug with respect to the teratogenic response on day eight only. The pretreatment with 0.25 mg/kg vindesine potentiated the radiation-induced malformation rate by a factor of 1.7, and the one with 0.35 mg/kg vindesine by a factor of 2.4.

Abnormalities, Drug-Induced↗

Variations of pion RBE in a volume with an asymmetric beam configuration.

The relative biological effectiveness for the radiation response of mouse jejunum for pions was determined in a clinically relevant asymmetric treatment geometry. A cylindrical volume of 570 ccm, with mouse holders in proximal and distal positions, was irradiated by spot scan technique with a sector of 31 concentric pion beams. The physical dose distribution within the treatment field was homogeneous and the average dose rate was 8.5 cGy/min. The aim was to determine RBE differences between the proximal and distal edge of the field and to compare it with the predictions. The RBE, relative to 200 kVp X-rays, was 1.3 for proximal position and 1.4 for the distal one. The results are in agreement with the calculations of the therapy planning computer program and with the microdosimetric characteristics at the two positions. The variation of the RBE is smaller than for the same field irradiated by a single pion beam.

Animals↗

[Current aspects in the evaluation of radiation risk: from the risk to organs to total injury risk (effective equivalent doses)].

For the estimation of the health risks of radiation in man by low radiation doses as well as to compare the man-made radiation exposure with the natural one, it is proved useful and necessary to estimate the effective dose-equivalent. It is not sufficient to take only into consideration the radiation exposure of bone marrow and gonads. Due to an external irradiation source as well as by incorporation of radioactive materials, various tissues and organs in the human body will simultaneously be exposed. This is best illustrated by the component of the "natural" radiation exposure with radon, attributable more or less to our living conditions. The incorporation of radon and its daughters in the lung with its cancer causing risk is not evaluated in the determination of the gonads and bone marrow dose. The effective dose-equivalent is being estimated for the evaluation of possible radiation risk by the carcinogenic and mutagenic effectiveness of radiation (stochastic radiation risk) with weighting factors. For the genetic risk solely 25% and for the somatic risk 75% are granted, whereas the risk factor "breast tissue" dominates.

Dose-Response Relationship, Radiation↗

Effect of different pion stopping volumes on the radiation response of mouse small intestine.

This radiobiological investigation was based on measurements of crypt cell survival in mouse small intestine when the animals were exposed to 5 cm3 (spot), 350 cm3 and 3010 cm3 (the latter two were spot scans) pion stopping volumes generated by the multi-channel Piotron of the Swiss Institute for Nuclear Research. The experimental data obtained indicate that there was a decrease in biological effectiveness when the pion treatment volume was enlarged, irrespective of whether the pion dose was delivered in a single exposure or in four fractions. The r.b.e. values for pion beams relative to 200 kVp X-rays for the different experimental conditions used in this study are presented. The phenomenon of decreasing biological effectiveness with increasing pion stopping volume may be attributed to the following two factors: (1) when the pion stopping volume is increased there is a corresponding dilution of the high l.e.t. component of the beam; (2) the biological test system used may be sensitive to radiation dose rate which varied by a ratio of about 20 for the pion volumes used in this study.

Animals↗

Possible damage of repair systems by Pi-mesons of different LET spectra.

Pi-meson experiments with repair-deficient spermatides and oocytes of Drosophila melanogaster have permitted a study of the LET dependence of the repair of different types of chromosomal lesions. The data show a distinction between primary events connected with fusion modalities (repair or misrepair) and those associated with no fusion. Repair deficiency increases the induction of chromosomal loss and dominant lethality (early damage) and decreases the induction of translocations (misrepair), perhaps responsible for late effects. The induction of nonfusion events is higher for pions compared to X rays and increases with mean lineal energy spectra, whereas the production of translocations is maximal at intermediate ionization density. The direct damage of repair systems by high-LET pions is postulated to explain these observations.

Animals↗