Late nonstochastic changes in pig skin after beta irradiation

Late radiation-induced changes in pig skin have been assessed following irradiation with beta-rays from a 22.5- or 15-mm-diameter 90Sr/90Y source and a 19- or 9-mm-diameter 170Tm source. Late damage, in terms of dermal atrophy, was assessed 2 years after irradiation from measurements of dermal thickness in irradiated and normal skin. After 90Sr irradiation maximum atrophy, a dermal thickness of 40-50% of the control value, occurred at a dose of approximately 40 Gy from the 22.5-mm source and approximately 75 Gy from the 15-mm source. In the case of 170Tm the 19- and 9-mm sources produced similar degrees of atrophy at equal doses. Maximum atrophy occurred at approximately 70 Gy, when the dermis was approximately 70% of the thickness of normal skin. Significant late tissue atrophy was seen at doses, from both types of radiation, which only produced minimal erythema in the early reaction. Such late reactions need to be taken into account when revised radiological protection criteria are proposed for skin.     

Morphological changes in the lungs after single whole-body irradiation in rabbits

Morphological changes in rabbit lungs were studied after whole-body nonuniform irradiation (24 Gy) the head and the abdomen being shielded. Acute pneumonitis was shown to develop between the 17th and the 24th day after irradiation. No pulmonary fibrosis was registered 60 days following irradiation. Embolised megakaryocytes were found in the lung capillaries between the 8th and the 24th day after irradiation.     

Structural changes of skin and amnion grafts for transplantation purposes following different doses of irradiation

An important part of the preparation of biological material for transplantation is sterilization. The aim of our study was to assess the impact of ionizing radiation on three types of biological tissues and the impact of different doses on cells and extracellular matrix. Three types of frozen tissues (porcine skin xenografts, human skin allografts and human amnion) were divided into five groups, control and groups according to the dose of radiation to which these samples were exposed (12.5, 25, 35 and 50 kGy). The tissue samples were fixed by formalin, processed by routine paraffin technique and stained with hematoxylin and eosin, alcian blue at pH 2.5, orcein, periodic acid schiff reaction and silver impregnation. The staining with hematoxylin and eosin showed hydropic degeneration of the cells of epidermis in xenografts by the dose of 12.5 kGy, in human skin it was observed by the dose of 35 kGy. The staining for elastic fibers revealed damage of fine elastic fibers in the xenografts dermis by the dose of 12.5 kGy, in the allografts by 35 kGy. Another change was the disintegration of basement membrane of epithelium, especially in the human amnion at the dose of 50 kGy. The silver impregnation visualized nuclear chromatin condensation mainly in human amnion at the dose of 12.5 kGy. Our results have shown that the porcine xenografts and human amnion were more sensitive to irradiation than the human skin. In the next phase of the project we will focus at more detailed changes in the tissues using immunohistochemical techniques.     

Schistosoma mansoni: dose-related tegumental surface changes after in vivo treatment with praziquantel

The in vivo effects of a range of concentrations of praziquantel (10, 25, 50, 100, 200 and 500 mg/kg body weight of mouse) on the tegumental surface of adult Schistosoma mansoni were studied using scanning electron microscopy. Worms were recovered from mice at 1 and 4 h post-treatment. In general, irrespective of the dose level, male worms exhibited more pronounced and extensive surface alterations which included surface bleeding, swellings, wrinkling and constrictions and surface lesions, particularly on the spined tubercles. In male worms, in particular, the number of worms exhibiting damage and the amount of tegumental surface damage depended, mainly, on the concentration of praziquantel, although, at any given dose level, the extent of the damage increased with time post-treatment.     

Growth delay in 9L rat brain tumor spheroids after irradiation with single and split doses of X rays

The response of 9L spheroids to irradiation with single and split doses of X rays has been investigated. Irradiation with single doses caused a dose-dependent decrease in spheroid growth rate, which eventually returned to the growth rate for unirradiated spheroids. This delay appeared to be related to cell survival. When spheroids were irradiated with two 4-Gy doses of X rays separated by various times the amount of growth delay was intermediate between that observed with single doses of 4 and 8 Gy. For relatively short times (15-90 min), recovery probably resulted from repair processes, but for longer times (up to 24 hr), recovery also appeared to depend on cellular redistribution and repopulation effects.     

Changes in osteoclasts after irradiation with carbon ion particles

We examined the effects of radiation on decreases in osteoclast numbers after regional irradiation of rats with carbon ions and gamma rays. Male Wistar rats were subjected to hind-leg irradiation with carbon ions (290 MeV/u) or gamma rays at doses of 15, 22.5, or 30 Gy. The effects of carbon ions and gamma rays on osteoclasts were studied using histologic and morphometric methods. At doses of 15 Gy and 22.5 Gy, osteoclast numbers increased transiently until day 5 after irradiation and then decreased rapidly in both the carbon ion and gamma ray irradiation groups. The carbon ion group showed reduced osteoclast size compared with the gamma ray group. Carbon ion irradiation had a more marked effect on osteoclast activity, and suppressed maturation to a greater extent than gamma irradiation. These observations suggest that carbon ion irradiation induces differential modulation of osteoclast growth factor expression.     

Quantification of rat retinal growth and vascular population changes after single and split doses of proton irradiation: translational study using stereology methods

This study quantified architectural and population changes in the rat retinal vasculature after proton irradiation using stereology. A 100 MeV conformal proton beam delivered 8, 14, 20 and 28 Gy as single and split doses to the whole eye. The vascular networks were prepared from retinal digests. Stereological methods were used to obtain the area of the retina and unbiased estimates of microvessel/artery/vein endothelial, pericyte and smooth muscle population, and vessel length. The retinal area increased progressively in the unirradiated, age-matched controls and in the retinas irradiated with 8 and 14 Gy, indicating uniform progressive retinal growth. No growth occurred after 20 and 28 Gy. Regression analysis of total endothelial cell number in all vessels (arteries, veins and capillaries) after irradiation documented a progressive time- and dose-dependent cell loss occurring over 15 to 24 months. The difference from controls was significant (P<0.01) after 28 Gy given in single and split doses and after 20 Gy given as a split dose (P<0.05). Total vessel length in microvessel was significantly shortened at 20 and 28 Gy compared to that of controls (P<0.05). No evident dose recovery was observed in the endothelial populations after split doses. At 10 Gy, the rate of endothelial cell loss, a dose parameter used to characterize the time- and dose-dependent loss of the endothelial population, was doubled.     

Circulatory and metabolic changes in expanded pig skin flaps

To evaluate circulatory and metabolic changes in pig skin during tissue expansion, the buttock skin of 12 pigs was expanded for 5 weeks. In a second operation, island buttock flaps were elevated bilaterally. Flap temperature, laser Doppler flow (LDF), and fluorescein penetration borders were recorded. Norepinephrine infusions were given twice. After cannulation of the external iliac veins, the total venous outflow from the flaps and metabolic parameters such as glucose and oxygen consumption and lactate production were measured bilaterally. No significant difference in fluorescein staining was found, but laser Doppler flow in the expanded tissue was higher than in nonexpanded skin, whereas the total flap blood flow was not significantly different. A flow reduction was seen in expanded flaps during norepinephrine infusion, whereas nonexpanded flaps showed a slightly increased blood flow. This adrenergic supersensitivity indicates that it is possible that not only surgical nerve section but also tissue expansion can result in sympathetic denervation. No differences in the metabolic parameters were observed.     

Time- and dose-related effects of gonadotropin-releasing hormone on growth hormone and gonadotropin subunit gene expression in the goldfish pituitary

The goldfish brain contains two molecular forms of gonadotropin-releasing hormone (GnRH): salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II). In a preliminary report, we demonstrated the stimulation of gonadotropin hormone (GtH) subunit and growth hormone (GH) mRNA levels by a single dose of GnRH at a single time point in the goldfish pituitary. Here we extend the work and demonstrate time- and dose-related effects of sGnRH and cGnRH-II on GtH subunit and GH gene expression in vivo and in vitro. The present study demonstrates important differences between the time- and dose-related effects of sGnRH and cGnRH-II on GtH subunit and GH mRNA levels. Using primary cultures of dispersed pituitary cells, the minimal effective dose of cGnRH-II required to stimulate GtH subunit mRNA levels was found to be 10-fold lower than that of sGnRH. In addition, the magnitudes of the increases in GtH subunit and GH mRNA levels stimulated by cGnRH-II were found to be higher than the sGnRH-induced responses. However, no significant difference was observed between sGnRH and cGnRH-II-induced responses in vivo. Time-related studies also revealed significant differences between sGnRH- and cGnRH-II-induced production of GtH subunit and GH mRNA in the goldfish pituitary. In general, the present study provides novel information on time- and dose-related effects of sGnRH and cGnRH-II on GtH subunit and GH mRNA levels and provides a framework for further investigation of GnRH mechanisms of action in the goldfish pituitary.     

A short term effect of homogeneous internal irradiation of the mouse lung with170Tm2O3 particles

Summary The short term effects on the free macrophage population in the mouse lung, following inhalation of thulium-170 oxide, have been studied, with a view to using the system as a model with which to compare the short term effects of inhomogeneous alpha irradiation.The clearance and distribution of thulium-170 was followed up to 44 days post inhalation. The mice had an initial lung burden (± SE) of 6.7 ± 0.5 µCi¹⁷⁰Tm/g of lung and the pattern of removal of this could be described by a single exponential of half time 31 ± 4 days.This exposure resulted in a uniform dose of about 24 Gy to the lung.The macrophage population was studied by counting cells lavaged from the lungs at intervals over the period of the experiment. The lung burden of¹⁷⁰Tm₂O₃ was found to decrease the free macrophage numbers by about a factor of 2 in 14 days with some slight recovery at 6 weeks post inhalation. It was found that nearly 50% of the activity in the lung lobes was removed by the lavages and that this fraction remained constant throughout.Environmental and Medical Sciences Division, A.E.R.E., Harwell     

One hundred percent tumor induction in mouse skin after repeated beta irradiation in a limited dose range

Repeated beta irradiation of the backs of mice three times a week with radiation doses of 250 to 1180 cGy per exposure induced 100% incidence of tumors. The incidence of skin tumors appeared to be determined by the total number of repeated exposures in this dose range. An abrupt delay in tumor emergence was observed when the radiation dose was reduced from 250 to 150 cGy per exposure, indicating the existence of a critical threshold. Mouse skin resembles human skin rather than rat skin in its response to radiation.     

Motor activity of rats after gamma irradiation in large doses

In experiments on 80 Wistar male rats their motor activity was studied using "Optovarimex" device which permitted to register the position of animals in space. The rats were subjected to total-body gamma-irradiation with doses of 6.5, 13, 50 and 100 Gy. The motor activity was studied 1, 24, 72 and 96 h following irradiation. Inhibition of the motor activity of animals was shown to depend upon radiation dose.