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.

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).

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.

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.

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.

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.

[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.

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).

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.

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.

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.

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.

Teratogenic interactions between cadmium and radiation in mice.

Mouse embryos were exposed to various doses of cadmium and/or X-rays on day 8 of gestation. The combined treatment exerted an antagonistic effect regarding the teratogenic action of the two agents.

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.

[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.

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.

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.

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.

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.

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).