Analysis of Data from a System of Assessment of the Gonadal Radiation Dose During Radiographic Procedures

The radiation hazard, if any, from diagnostic x-ray examinations was assessed in a study divided into three phases: (1) the gathering of data to allow estimation of the total gonadal dose received by each patient; (2) the accumulation of the individual and accumulative gonadal-dose totals on a large group of patients; (3) the examination and follow-up of patients who had received a substantial gonadal dose to determine any relationship between small recurring doses of ionizing radiation and various indices of somatic and genetic damage.The mean gonadal dose received by females was much higher than that received by males—1012 mr. as compared to 310 mr. Of 7021 individuals in this study, only 428 (6.1%) received 2 r. or more during the three-year test period. No definite conclusions as to radiation hazard could be made. A system, however, has been developed which, if continued, could eventually produce this basic information.     

Medical Radiation to Children with Congenital Heart Disease

A retrospective analysis was made of the source of medical radiation received by 25 children who were investigated by cardiac catheterization techniques and followed in the Cardiac Outpatient Clinic of the Health Centre for Children, Vancouver General Hospital. The source of radiation was analyzed. The r dose per year received from plane films averaged 0.05 r, from cardiac fluoroscopy 6.7 r, and from catheterization and angiocardiography studies 1.58 r per year. In six of the 25 children, radiation doses to the thorax exceeded the LD₅₀ for adult humans. In these six patients 95.8% of the radiation received was during cardiac fluoroscopy. Routine fluoroscopy for the radiological re-evaluation of pediatric patients with congenital heart disease should be replaced by plain chest radiographs.     

Organ doses from radiation therapy in atomic bomb survivors

Previous surveys of radiation therapy among the Life Span Study (LSS) population at the Radiation Effects Research Foundation (RERF) revealed that 1,670 (1.4%) of the LSS participants received radiation treatments before 1984. The data on therapeutic radiation doses are indispensable for studying the relationship between radiation treatments and subsequent cancer occurrences. In this study, the radiation treatments were reproduced experimentally to determine the scattered radiation doses. The experiments were conducted using a female human phantom and various radiation sources, including a medium-voltage X-ray machine and a (60)Co gamma-ray source. Doses were measured using thermoluminescence dosimetry and ionization chambers. Radiation doses were determined for the salivary glands, thyroid gland, breast, lung, stomach, colon, ovary and active bone marrow. The results have been used for documenting the organ doses received by patients in previous surveys. The contribution of therapeutic irradiation to the occurrence of chromosome aberrations was studied using data on doses to active bone marrow from both radiation treatments and atomic bomb exposures in 26 RERF Adult Health Study participants. The results suggest that radiation treatments contributed to a large part of their frequencies of stable-type chromosome aberrations. The therapeutic radiation doses determined in the present study are available for investigating the effects of therapeutic irradiation on the subsequent primary cancers among atomic bomb survivors who received radiation treatments.     

Differences between male and female protogonia in chick embryos before sex differentiation of the gonads

The sex of chick embryos is diagnosed by cyto-karyological methods on skin fragments of 2-7 days' incubation before gonadal sex differentiation. In 44 males and 42 females statistical analyses have been made of the number and dimension of the germ cells, and of the volume of the gonadal primordia. Moreover an ultrastructural study has been made on the germ cells colonizing the genital ridges (70-hours of incubation). Early differences between the sexes have been found regarding: earlier numerical increase of CGs in the left gonadal primordium of the females; larger primordial germ cells in the female; the same cytological characteristics at ultrastructural level.     

15 years after the accident at the Chernobyl Nuclear Power Plant

Health effects as a result of the accident at the Chernobyl nuclear power plant occurred in 1986 are considered in the paper. Wrong prognosis of the health effects with respect to mortality and morbidity among the population exposed to low radiation doses is shown. Proven increase in thyroid cancer cases among people who were children aged from 0 to 18 at the time of the accident is shown. Linear relationship between thyroid cancer cases and dose to thyroid ranged from 0.2 to 4.0 Gy is considered. An additional absolute risk of thyroid cancer in children varies in the range 1.9-2.6 cases per 10(4) person-year Gy. During the fifteen years following the accident no cases of acute and chronic radiation sickness have been revealed because the population living in contaminated areas received low radiation doses. Also, exposures to low radiation doses did not result in excess of malignant tumors among population. In some cases the outcomes of acute radiation sickness were as follows: radiation damages to the skin, cancer cataracts, development of oncopathology.     

Morphologic study of tissue basophils of the skin in rats after acute local irradiation

A comparative morphological study was made of tissue basophils (TB) of rat skin at remote times (40, 70, 140, and 360 days) following single local exposure to soft and hard X-radiation with the doses at the skin surface of 15, 20, and 30 Gy. The TB response was maximum in the subepidermal and supramuscular layers of friable connective tissue. Changes in a median TB diameter were of a phase nature and a function of radiation dose absorbed in the skin layers under study.     

In situ biological dose mapping estimates the radiation burden delivered to 'spared' tissue between synchrotron X-ray microbeam radiotherapy tracks

Microbeam radiation therapy (MRT) using high doses of synchrotron X-rays can destroy tumours in animal models whilst causing little damage to normal tissues. Determining the spatial distribution of radiation doses delivered during MRT at a microscopic scale is a major challenge. Film and semiconductor dosimetry as well as Monte Carlo methods struggle to provide accurate estimates of dose profiles and peak-to-valley dose ratios at the position of the targeted and traversed tissues whose biological responses determine treatment outcome. The purpose of this study was to utilise γ-H2AX immunostaining as a biodosimetric tool that enables in situ biological dose mapping within an irradiated tissue to provide direct biological evidence for the scale of the radiation burden to 'spared' tissue regions between MRT tracks. Γ-H2AX analysis allowed microbeams to be traced and DNA damage foci to be quantified in valleys between beams following MRT treatment of fibroblast cultures and murine skin where foci yields per unit dose were approximately five-fold lower than in fibroblast cultures. Foci levels in cells located in valleys were compared with calibration curves using known broadbeam synchrotron X-ray doses to generate spatial dose profiles and calculate peak-to-valley dose ratios of 30-40 for cell cultures and approximately 60 for murine skin, consistent with the range obtained with conventional dosimetry methods. This biological dose mapping approach could find several applications both in optimising MRT or other radiotherapeutic treatments and in estimating localised doses following accidental radiation exposure using skin punch biopsies.     

External radiation doses from <Superscript>137</Superscript>Cs to frog phantoms in a wetland area: in situ measurements and dose model calculations

For assessment of external radiation doses to frogs in a wetland area contaminated with ¹³⁷Cs, frog phantoms were constructed from polymethyl methacrylate (PMMA). The frog phantoms contained thermoluminescence (TL) chips and were used in situ at two study sites to measure doses. To test if higher doses are received by the sensitive skin of frogs, extra-thin TL chips were applied close to the surface of the frog phantoms. In addition, the measured doses were compared with those calculated on the basis of soil sample data from the wetland multiplied with dose-conversion coefficients from the US Department of Energy’s RESRAD-BIOTA code and from the ERICA assessment tool. Measured doses were generally lower than those calculated to ellipsoids used to model frogs. Higher doses were measured at the frog phantoms’ surfaces in comparison to inner parts at one of the two sites indicating that the frogs’ thin skin could receive a higher radiation dose than expected. In the efforts to assure protection of non-human biota, in situ measurements with phantoms provide valuable dose information and input to dose models in site-specific risk assessments of areas contaminated with radionuclides.     

The use of 'top-up' experiments to investigate the effect of very small doses per fraction in mouse skin

The partial tolerance type of 'top-up' experiment has been investigated to determine the resolution of this approach for studying the damage to mouse skin from very small doses of X-rays and neutrons. The effect of 20 fractions, each as small as 0.10 Gy of X-rays or of 0.05 Gy of neutrons, can be detected if 3 MeV neutrons are used as the 'top-up' reference radiation. This capability results from the almost linear underlying dose-response curve and highly reproducible dose-effect relationship for the low energy neutrons. The data fit the linear quadratic model of dose fractionation for X-rays down to fractional doses of 0.75 Gy, but at lower doses there is a trend towards an increase in the skin radiosensitivity. Modelling shows that this might be consistent with a sub-population of the cells showing an exceptional radiosensitivity, and a replenishment of this subpopulation occurring in the 8 h between small dose fractions. More experiments are needed at very low doses in order to confirm this hypothesis for skin and for other tissues.     

Accumulation, activation and interindividual variation of the epidermal TP53 protein in response to ionizing radiation in organ cultured human skin

In this study, we examined effects of low-dose ionizing radiation on organ cultured human foreskin and, in particular, on the epidermis. Diagnostic, therapeutic, natural environmental and incidental exposures to moderate to low doses of radiation are inevitable and, although information on cultured cells continues to accumulate, little is known about the effects of low-dose radiation on human tissues. Our hypothesis is that ex vivo organ cultured foreskin is a simple and reliable model to study the biochemical effects of low-dose radiation exposure on skin. A model such as this will aid in the identification and quantification of low-dose radiation-induced changes in proteins in human skin and may be useful in the development of a precise, non-invasive, and reliable assay of exposure. In this work, several aspects of skin responses to culture conditions and radiation were examined. The responses of epidermal TP53 from organ cultured skin irradiated in medium with and without serum were found to be similar. TP53 levels in organ cultured neonatal foreskin epidermis were then examined for baseline TP53 expression. After an initial increase at 4 h, the TP53 D01 signal returned to low steady-state levels for at least 72 h. Irradiated skin samples from different individuals revealed variations in the TP53 D01 signal. The dose and temporal response of dermis and epidermis to radiation were examined by Western blotting from 0 to 24 h after exposure. After irradiation and incubation, the epidermis was removed and assayed by Western blotting and was found to have increases in the TP53 D01 epitope and the TP53 phosphoserine 15 (TP53-S15p) epitope that reached a maximum at about 3 h. In the epidermis, doses of 1-5 cGy of radiation were detectable with the TP53 D01, and CDKN1A antibodies and doses greater than 10 cGy were detectable with the TP53-S15p antibody. When the dermis was compared to epidermis, it was found that dermis had a smaller response to radiation and more phosphorylated TP53.     

The experience of FISH technique application for reconstruction of individual radiation doses in Chernobyl liquidators in the framework of Ukrainian-American project "Leukemia"

The results of proper investigations received under the cytogenetic examination of 225 persons (control groups, Chernobyl liquidators exposed to different radiation doses, oncogematology patients) had been summarized and analyzed. The conclusion concerning possibilities and limitations of FISH technique usage for retrospective biodosimetry of human radiation exposure has been presented.     

Speculations on the origin of the ill-effects associated with the use of visual display terminals

There are increasing reports of a wide variety of unexplained ill-effects associated with the occupational use of visual display terminals (VDTs); these include psychological complaints such as headache, irritability, and fatigue, musculoskeletal pains, dry or burning eyes, deteriorating eyesight, cataracts, facial dermatitis, and pregnancy abnormalities. Many VDTs emit near-ultraviolet (UV-A) radiation in amounts ranging from 200 to 1500 times less than the present U.S. safety standard of 1.0 X 10(-3) W/cm2. Although the possibility of a radiation hazard from VDTs is widely discounted, various points of circumstantial evidence are marshalled in this paper in support of the hypothesis that prolonged exposure to even these low amounts of UV-A radiation may result in progressive increases in sensitivity to UV-A and in cumulative biologic damage. It is further proposed that UV-A produces the ill-effects by catabolizing vitamin A in skin and plasma into highly active metabolites, the gradual accumulation of which results in an endogenous form of vitamin A intoxication. In addition to producing the skin and systemic effects of hypervitaminosis A, these metabolites presumably enter the fetal circulation, leading to pregnancy abnormalities similar to those associated with high doses of the vitamin for the treatment of skin disorders.     

4-Thiothymidine sensitization of DNA to UVA offers potential for a novel photochemotherapy

Photochemotherapy, in which ultraviolet radiation (UVR: 280-400 nm) or visible light is combined with a photosensitizing drug to produce a therapeutic effect that neither drug or radiation can achieve alone, is a proven therapeutic strategy for a number of non-malignant hyperproliferative skin conditions and various cancers. Examples are psoralen plus UVA (320-400 nm) radiation (PUVA) and photodynamic therapy (PDT). All existing photochemotherapies have drawbacks - for example the association of PUVA with the development of skin cancer, and pain that is often associated with PDT treatment of skin lesions. There is a clear need to develop alternative approaches that involve lower radiation doses and/or improved selectivity for target cells. In this review, we explore the possibility to address this need by exploiting thionucleoside-mediated DNA photosensitisation to low, non toxic doses of UVA radiation.     

Methods for exposure of laboratory animals to ultraviolet radiation

Two different sources of ultraviolet B (UVB) radiation, an electronically controlled UVB exposure unit, containing FS40 tubes, and a hand-held Kromayer lamp, were evaluated for actual irradiance in W/m2 and spectra (physical dosimetry and biological dosimetry (skin effects in rodents)). The technical studies of the FS40 sources demonstrated that the flux intensity of the lamps could be changed electronically, without affecting the spectrum. Thus it was possible to standardize UVB exposure electronically. The biologically effective doses of these sources were analysed in RIV-Tox Wistar rats and BALB/c mice. After low doses of UVB radiation, histopathological changes such as acanthosis, hyperkeratosis and dermal inflammation were observed in the skin without the presence of major side effects such as erythema and oedema. After higher doses of UVB radiation erythema and oedema were clearly visible. Quantitative studies showed that the minimal erythema dose, as a biological parameter, correlated well to the emission in J/m2. In addition, biological parameters such as acanthosis and inflammation in the skin correlated well to the actual exposure in J/m2 and were sensitive biomarkers for UVB-induced skin toxicity. Thus, in addition to minimal erythemal doses, acanthosis and inflammation may also be applied as biologically relevant doses for studies of the biological effects of UVB radiation.     

Analysis of the epidemiological data concerning radiation carcinogenic effects and approaches to the low doses' upper limits determination in the aspect of a threshold of the unhealthy influences of ionizing radiation

The analysis of the epidemiological data regarding cancer mortality in cohorts of Japanese A-bomb survivors and Chermobyl liquidators exposed to different doses suggests that there are good reasons for recognizing the threshold of the radiocarcinogenic effect in the region of about 200 Gy (mSv). The analysis of solid cancer mortality in Japanese cohort, which exceeded the expected one in a dose diapason of 5-200 mSv, revealed a (quasi) plateau in a dose-effect curve and led to the conclusion that the nature of the overshoot is non-radiogenic. The analysis of supposedly dose dependent leucosis incidence in the limited low dose diapason in the Chernobyl cohort showed that the real coefficient of the excess absolute or relative radiation risk could not be received in the case because the larger part curve was placed under the control level. In supporting the principle of single hit in a cell nucleus as a base of microdosimetric determination of low radiation doses, the approach to objective delimitation between low, intermediate and high doses regions has been proposed. The low doses upper limit of sparse ionizing radiation for cell nucleus of 8 microns in diameter has been evaluated as 0.65 mGy. It can serve for evaluation of the dose rate threshold regarding the safe chronic radiation levels in the environment.     

Late occurring lesions in the skin of rats after repeated doses of X-rays

Late radiation damage, characterized by atrophy and necrosis in the skin and subcutaneous tissues, has been demonstrated in both the tail and feet of rats. The incidence of necrosis increased with total dose. These total doses, in the range 72-144 Gy, were given as 4-8 treatments of 18 Gy, each dose separated from the next by an interval of 28 days. This treatment protocol minimized acute epithelial skin reactions. The same regime applied to the skin on the back of rats resulted in a very severe acute reaction occurring after the second to fifth dose of 18 Gy. This was surprising since back skin, like tail skin, is less sensitive to large single doses of radiation than that of the foot. The late radiation reaction in the foot and tail of rats are compared and contrasted with other attempts to assess late effects in rodent skin and with late changes seen in pig skin.     

Response of rat skin to high-dose unidirectional x-ray microbeams: a histological study

There is growing interest in evaluating microbeam radiation therapy as a potential clinical modality. Microbeam radiation therapy uses arrays of parallel, microscopically thin (<100 microm) planes of synchrotron-generated X rays (microplanar beams, or microbeams). Due to the relatively low beam energies involved in microbeam radiation therapy (a median beam energy of 120 keV was used in the present study), the dose penetration of microbeams in tissue is lower than that used in conventional radiotherapy. This lower energy necessitates using a significantly elevated dose to the skin's surface during clinical microbeam therapy to ensure an adequate dose distribution in the target tumor. The findings of the present study, using a rat skin model, indicated that the skin had an extremely high tolerance to microbeam radiation at doses considerably in excess of those that were therapeutically effective in preclinical studies. A histological study was undertaken to evaluate the biological mechanisms underlying this high tolerance. The irradiation configuration employed single-exposure, unidirectional microbeams 90 microm wide, with 300 microm beam spacing on-center. The in-beam skin-surface absorbed doses were in the range 835-1335 Gy. Monte Carlo simulations of the dose distribution indicated that the "valley" dose, i.e. the radiation leakage between adjacent microbeams, was about 2.5% of the in-beam dose. The high tolerance of the rats' skin to microbeams and the rapid regeneration of the damaged segments of skin were attributed to the surviving clonogenic cells situated between the adjacent microplanar beams. In the epidermis, clonogenic cells in the hair follicular epithelium appeared to play a key role in the regeneration process.     

Laparoscopy and Gonadal Biopsy for Assessment of Gonadal Function in Primary Amenorrhoea

Twenty patients with primary amenorrhoea have been investigated by laparoscopy and gonadal biopsy, endocrine and chromosomal studies. Laparoscopy and gonadal biopsy made the major contribution to the diagnosis, prognosis, and management of the patients and provided a method for study of the functional anatomy of the ovary.     

Radiation-induced bystander effects in the Atlantic salmon (salmo salar L.) following mixed exposure to copper and aluminum combined with low-dose gamma radiation

Very little is known about the combined effects of low doses of heavy metals and radiation. However, such “multiple stressor” exposure is the reality in the environment. In the work reported in this paper, fish were exposed to cobalt 60 gamma irradiation with or without copper or aluminum in the water. Doses of radiation ranged from 4 to 75 mGy delivered over 48 or 6 h. Copper doses ranged from 10 to 80 μg/L for the same time period. The aluminum dose was 250 μg/L. Gills and skin were removed from the fish after exposure and explanted in tissue culture flasks for investigation of bystander effects of the exposures using a stress signal reporter assay, which has been demonstrated to be a sensitive indicator of homeostatic perturbations in cells. The results show complex synergistic interactions of radiation and copper. Gills on the whole produce more toxic bystander signals than skin, but the additivity scores show highly variable results which depend on dose and time of exposure. The impacts of low doses of copper and low doses of radiation are greater than additive, medium levels of copper alone have a similar level of effect of bystander signal toxicity to the low dose. The addition of radiation stress, however, produces clear protective effects in the reporters treated with skin-derived medium. Gill-derived medium from the same fish did not show protective effects. Radiation exposure in the presence of 80 μg/L led to highly variable results, which due to animal variation were not significantly different from the effect of copper alone. The results are stressor type, stressor concentration and time dependent. Clearly co-exposure to radiation and heavy metals does not always lead to simple additive effects.     

Modeling radiation dose and effects from internal emitters in nuclear medicine: from the whole body to individual cells.

In nuclear medicine, proper application of radiation protection principles depends on balancing the potential risks of exposure to ionizing radiation against its possible benefits. Average doses to organs, in diagnostic or therapeutic applications, are not always representative of the doses received at the tissue or cellular level. Therefore, understanding of the relationship between the overall biological effect and absorbed dose delivered by the radiopharmaceutical may require study of doses at the organ, tissue, or cell level. In this paper, we review current models for radiation dose assessment, with consideration of the different models and assumptions employed for study at all levels of investigation.