The effect of ionizing radiation on the vascular bed of the skin in ontogeny. The function of the microcirculatory bed of the skin in the fetuses of white rats sublethally irradiated]

Albino female rats were exposed to X radiation (5 Gy, 180 kV, 10 mA, filter 0.5 mm Cu) on days 10-15 of pregnancy. After 3 and 7 days they were sacrificed (under ether anesthesia) and fetuses were extracted. The status of the lympho- and hemomicrocirculatory beds (LMCB and HMCB) of the fetus back skin was studied by the macro- and microscopic methods. As early as day 3 of radiation sickness the diameter of LMCB vessels increased by 1.4-1.9 times, whereas changes in GMCB were less pronounced. On day 7, there was a progressive increase in dilatation of LMCB vessels, alongside with the narrowing of large units (arteries and veins). The development of the connective framework of the fetus skin was retarded.     

The effect of ionizing radiation on the phospholipid content of fetal and maternal liver mitochondria at different stages of pregnancy]

A single exposure of pregnant rats to 1 and 2 Gy radiation on days 3, 13 and 17 of reception changes the phospholipid content in membranes of liver mitochondria of fetus and maternal body. The changes are particularly pronounced on day 3 of reception: as the embryo grows the decline in the phospholipid content from the control level decreases.     

Reaction of posterity of two generations after exposure of pregnant Wistar rats to low dose irradiation during the period of fetus formation. Development of the first generation posterity

Whole-body single exposure of female Wistar rats to 0.25, 0.5 and 1 Gy of gamma-rays (dose rate of 0.03 cGy/s) on the 10th day of pregnancy (a period of formation of the reproductive system in fetus) was carried out. To study irradiation consequences on the antenatal and postnatal development of the progeny 220 females, 700 19-day-old fetuses and about 1100 young rats were examined. The antenatal development of the progeny of the first generation was significantly impaired after the exposure to 1 Gy. However even less radiation doses resulted in a pronounced tendency to higher rates of intrauterine death and a lower number of live fetuses. Significant deviatins in the postnatal development of the first generation progeny were found after the exposure to 0.5 Gy, although the exposure to 0.25 Gy led to a higher rate of postnatal death and a less number of newborns in the litter.     

The effect of joint, radiation and chemical lesions in rats on their reproductive function]

In experiments with rats exposed to the combined radiation and chemical effects it was shown that fertilization of an ovum and the development of fetus did not vary from these indices in the controls. Viability of sucking rat pups isolated from poison did not vary from the controls as well. Sensitivity of posterity to the toxic effect of chlorophos and lindane was found to increase.     

Modifying influence of iodine deficiency on radiation damage to the fetus (review)

It known an oppressing action of radiation, including radioactive iodine isotopes on the reproductive system and fetus development. There are clinical data on a negative influence of iodine deficiency on the course of pregnancy and fetus development resulting from hormonal disfunction of thyroid gland and a mother-fetus system. There are no data about a character and mechanisms of interaction of radiation and iodine endemia at the combined action on the gonads and fetus. The urgency of this problem is caused by the fact that many regions of the country are characterized to some extent by iodine deficiency in local food and water (in Russian Federation such regions make approximately 50% of territories), and the opportunity of radiation accidents at nuclear plants with contamination of the environment with products of nuclear division (significant part of which is radioactive iodine isotopes is an objective reality. The analysis of a few published and own experimental data allows us to conclude that the combined influence of an external gamma-irradiation and iodine deficiency on reproductive function has a synergic character.     

Experience in using cystamine for decreasing radiation disorders in Wistar rat embryogenesis

In experiments on 340 primigravida Wistar rats and 1557 young rats of the first generation a study was made of toxicity and radioprotective efficiency of single subcutaneous injection of 100 mg/kg cystamine on days 3, 11 and 19 of pregnancy. In the control animals, the preparation caused different changes in the pregnancy course, delivery and postnatal development of posterity. The radioprotective properties of the preparation were only manifested when embryos were exposed to 3 Gy radiation (a lethal dose) during the preimplantation period, and it was less effective during the periods of organogenesis and fetus formation.     

Teratogenic effects of incorporated radionuclides

Experimental data on teratogenic effects induced by incorporated alpha, beta and gamma-emitters were analyzed. It was found that the radioactive substances as well as external irradiation induced teratogenic effects. Teratogenesis caused by incorporated radionuclides has some peculiarities compared to the effect caused by fetus exposure to external radiation. These peculiarities are related to the fact of the limited penetration of incorporated radionuclides via placenta barrier so the radiation fetal doses are accumulated within long period of time and radiation dose rates are relatively low. The exposure to incorporated radionuclides does not induce severe developmental defects. Most frequent developmental defects of fetus include its death, general retardation of the development and growth. In such case the earlier pregnancy term was affected by radionuclide the more severe fetal damages occur in fetus because of the gradual increase of absorbed dose even in case of single intake of radionuclide. RBEs of radionuclides if compared to that for external gamma radiation are evaluated as follows: 2-4 (tritium oxide), 20 (241Am), 50 (238Pu) and 3-5 (131I in thyroid).     

Postnatal effects in children irradiated during the intra-uterine development, as a result of failure at the Chernobyl NPP

Somatic and genetic effects at children who have undergone the influence of ionizing radiation during in utero development and at the subsequent stages ontogenesis are investigated, in view of dozes of the general irradiation and equivalent dozes of an irradiation of red bone brain. 1144 children were examined: 1st group consisted of children who have been born from women pregnant at the moment of failure, evacuated from Pripyat; 2nd group included children who have been born from women pregnant at the moment of failure, stayed to live in a zone of the strict radiation control; 3rd group was the control group--children who have been born in 1986, living in safe region of the Ukraine according to radiation conditions. The presence of direct correlation link between quantity of small anomalies of the development and the total radiation dose of the fetus (R = 0.61, p < 0.002) and inverse link with fetus age at the moment of radiation factor effect (R = -0.53, p < 0.003) has been established. Significant correlation links between the total radiation dose and the level of children health (R = 0.45, p < 0.03); the equivalent radiation dose of the red bone marrow and the frequency of damages in the chromosomal apparatus of the somatic cells (1st group--R = 0.51, p < 0.02; 2nd group--R = 0.62, p < 0.002) have been revealed.     

A unique combination of infrared and microwave radiation accelerates wound healing

Light or electromagnetic radiation has been reported to enhance wound healing. The use of selected spectra, including infrared and microwave, has been described; however, no studies to date have examined the potential benefit of combining these spectra. In this study, a device that emits electromagnetic radiation across both the infrared and microwave ranges was used. To test the effects of this unique electromagnetic radiation spectrum on wound healing, two clinically relevant wound-healing models (i.e., tensile strength of simple incisions and survival of McFarlane flaps) were selected. After the creation of a simple full-thickness incision (n = 35 rats) or a caudally based McFarlane flap (n = 33 rats), animals were randomly assigned to one of three treatment groups: untreated control, infrared, or combined electromagnetic radiation. Treatment was administered for 30 minutes, twice daily for 18 days in animals with simple incisions, and 15 days in animals with McFarlane flaps. The wound area or flap was harvested and analyzed, blinded to the treatment regimens. A p value of less than 0.05 obtained by analysis of variance was considered to be statistically significant. Animals receiving combined electromagnetic radiation demonstrated increased tensile strength (2.62 N/mm2) compared with animals receiving infrared radiation (2.36 N/mm2) or untreated controls (1.73 N/mm2, p < 0.001). Animals with McFarlane flaps receiving combined electromagnetic radiation had increased flap survival (78.0 percent) compared with animals receiving infrared radiation (69.7 percent) and untreated controls (63.1 percent, p < 0.01). Thus, combined electromagnetic radiation provided a distinct advantage in wound healing that might augment current treatment regimens.     

Effects of external beam irradiation on the TRAM flap: an experimental model

The rat model of the transverse rectus abdominis musculocutaneous (TRAM) flap was used in the present study to determine the effects of external beam radiation on myocutaneous flap histology and pathophysiology. A total of 57 adult Sprague-Dawley rats underwent a TRAM procedure. A pilot study with 17 animals was first performed to determine proper radiation dosages, and the remaining 40 rats were then used in the definitive study. In half of the definitive study group, the flaps were subjected to fractionated doses of external beam radiation, whereas the other half served as controls. Six weeks after the last radiation dose, all animals were killed and the flaps were harvested for mechanical assessment and histopathologic evaluation. All TRAM flaps survived in both groups. The irradiated and nonirradiated flaps were minimally distinguishable in viscoelastic properties, as well as by histopathologic examination. Growth of the flap in the irradiated animals was significantly diminished (48 percent average surface area increase in irradiated flaps, versus 92 percent increase in nonirradiated flaps, p < 0.05). These findings suggest that the myocutaneous flap is relatively resistant to some of the known adverse affects of radiation on living tissues.     

Effect of position in the uterus on the fetal weight of the 21st day of pregnancy in the unilaterally ovariectomized rat

Effects of intrauterine position of the fetuses on the weight of fetal sac, fetus and placenta were investigated on the 21th day of unilaterally (right) ovariectomized pregnant Wistar strain rats. Results were obtained as follows. 1. Litter size was negatively correlated with the mean weights of fetal sac and fetus. 2. The mean weights of male fetal sac and fetus were heavier than those of female ones, while there was no difference in the weight of placenta between male and female. 3. The mean weights of male fetal sac and fetus positioning ovarian end (OV) were lighter than those of ones at the other positions. And the highest frequency of the lightest weight of live fetuses was demonstrated at OV position. 4. The mean weights of male fetal sac and fetus positioning between two males (2M) were heavier than those of ones positioning not next to male (0M). And the mean weight of 2M female fetal sac was heavier than those of 0M one. 5. The mean weights of fetal sac and fetus positioning next to resorbed fetus were heavier than those of ones positioning not next to resorbed fetus.     

The inhibition of dopamine synthesis in fetuses changes the pattern of T-lymphocyte maturation in the thymus of adult rats

The mRNA for dopamine receptors of type D1, D3, D5, but not type D2, was detected in the thymus of rats starting from day 16 of embryonic development (E16). Dopamine at concentrations of 10^–8–10^?6 M inhibited fetus thymocyte response to mitogen, confirming the functionality of the receptors and the possibility of a direct effect of dopamine on the developing thymus. Pharmacological inhibition of catecholamine synthesis in the crucial period of thymus development leads to long-term changes in the T-system immunity due to increased production of natural regulatory T-lymphocytes. The presence and functional activity of dopamine receptors in the fetal thymus indicates its ability to influence the development of the immune system of rats during ontogeny.     

Estimation and reduction of the radiation dose to the fetus from external-beam radiotherapy

The appearance of a malignant disease during pregnancy is relatively rare. The use of external-beam radiation therapy is limited to non-pelvic tumors which are usually located above the diaphragm. However, supradiaphragmatic radiotherapy unavoidably exposes the fetus to secondary radiation due to head leakage, scatter from the machine and scatter produced inside the patient. This fetal exposure may be associated with an elevated risk for the development of deterministic harmful effects and/or carcinogenesis. The decision about the administration of radiotherapy in a pregnant patient is influenced by the fetal dose which must always be estimated before the patient’s treatment course. The methods employed for fetal dosimetry in external-beam radiotherapy are described in this review study. Direct dose measurements using thermoluminescent dosemeters or large ionization chambers placed on physical phantoms may be used. Monte Carlo simulations on computational phantoms may also provide accurate fetal dose calculations. The physical and/or computational phantoms need to simulate the full-scatter geometry of the pregnant patient. Typical fetal dose values attributable to radiation therapy for brain tumors, head and neck cancer, breast carcinoma and Hodgkin lymphoma at the first, second and third trimesters of gestation are presented. The effectiveness of different shielding devices for fetal dose reduction in radiotherapy is discussed. The effect of the dimensions and setup of the shielding material on the radiation dose received by the fetus is described. Moreover, practical methods for reducing the fetal dose by selecting the appropriate irradiation parameters are presented.     

Teratogenicity of the antiallergic Sm 857 SE in rats versus rabbits

Sm 857 SE is an antiallergic drug chemically described as 11-Oxo-11H-pyrido(2,1-b)quinazoline-2-carboxylic acid that has activity against allergic bronchoconstriction in animal models. The purpose of this study was to investigate the teratogenic potential in pregnant rats and rabbits when administered during the critical period of organogenesis. The drug was suspended in aqueous 0.25% carboxymethylcellulose (CMC) solution. Daily doses of 20, 90, or 400 mg/kg were given orally by gavage to rats on days 7 through 17 of gestation and to rabbits on days 6 through 18. Two additional studies were done in rats dosed with 400 mg/kg, and with 90, 200, or 400 mg/kg, respectively. Doses of 20, 90, and 200 mg/kg had no meaningful effects on maternal animals of either species or on their offspring. A dose of 400 mg/kg was maternally toxic in rats as shown by the effects on body weight and food consumption. Among pregnant rabbits, two deaths and three miscarriages occurred at this dose. In rats, 400 mg/kg caused embryonic death, retarded fetal development, and two specific malformations, namely microphthalmia and vertebral-costal defects. A mild teratogenic action of 400 mg/kg also occurred in the first additional study but not in the second one. There was, however, one anophthalmia in a rat fetus of the 90 mg/kg group. In rabbits, no embryotoxic or teratogenic effects were observed. These species differences were explained by the concentration and protein binding in maternal serum as well as by the relatively high concentration of 14C-Sm 857 SE in the rat fetus.     

Change in the percent of lactate dehydrogenase isoenzyme level in testes of animals exposed to superhigh frequency radiation

The content of six lactate dehydrogenase isoenzymes in testes of rats exposed to electromagnetic field of 3-cm wavelength range was studied. The changes in their percent contents were found to be inhomogeneous compared with control. It is assumed that electromagnetic radiation affects the organs of the human urinogenital system. The results can be used for estimating the safety of persons professionally exposed to electromagnetic radiation of the industrial frequency range and in the therapy of diseases of the urinogenital system.     

Paternal obesity induces epigenetic aberrations and gene expression changes in placenta and fetus

Paternal epigenome regulates placental and fetal growth. However, the effect of paternal obesity on placenta and its subsequent effect on the fetus via sperm remains unknown. We previously discovered abnormal methylation of imprinted genes involved in placental and fetal development in the spermatozoa of obese rats. In the present study, elaborate epigenetic characterization of sperm, placenta, and fetus was performed. For 16 weeks, male rats were fed either control or a high-fat diet. Following mating studies, sperm, placenta, and fetal tissue were collected. Significant changes were observed in placental weights, morphology, and cell populations. Methylation status of imprinted genes—Igf2, Peg3, Cdkn1c, and Gnas in spermatozoa, correlated with their expression in the placenta and fetus. Placental DNA methylating enzymes and 5-methylCytosine levels increased. Furthermore, in spermatozoa, DNA methylation of a few genes involved in pathways associated with placental endocrine function—gonadotropin-releasing hormone, prolactin, estrogen, and vascular endothelial growth factor, correlated with their expression in placenta and fetus. Changes in histone-modifying enzymes were also observed in the placenta. Histone marks H3K4me3, H3K9me3, and H4ac were downregulated, while H3K27me3 and H3ac were upregulated in placentas derived from obese male rats. This study shows that obesity-related changes in sperm methylome translate into abnormal expression in the F1-placenta fathered by the obese male, presumably affecting placental and fetal development.     

Mobile shielding evaluation on the fetal dose during a breast radiotherapy using Monte Carlo simulation

PurposeEvaluation of the out-of-field dose is an important aspect in radiotherapy. Due to the fetus radiosensitivity, this evaluation becomes even more conclusive when the patient is pregnant. In this work, a linear accelerator Varian Clinac 2100c operating at 6 MV, a pregnant anthropomorphic phantom (Maria), and different shields added above the abdominal region of the phantom were used for the analysis based on MCNPX. Methods: The simulations were performed for the medial and lateral projections, using either an open field collimation (10×16 cm²) or a multileaf collimator. The added shields (M1 and M2) were designed based on models proposed by Stovall et al. [1], intending to reduce the deposited dose on the fetus and related structures. Results: The presence of the shields showed to be effective in reducing the doses on the fetus, amniotic sac, and placenta, for example. A reduction of about 43% was found in the dose on the fetus when M2 was added, using the open field collimation, in comparison with the situation with no shield, being the lateral projection the main responsible for the dose. The use of MLC significatively reduced the doses in different structures, including on the fetus and amniotic sac, for example, in comparison to the open field situation. A slight increment on the dose in organs such as the eyes, thyroid and brain was found in both collimation systems, due to the presence of the shields. The contribution of the leakage radiation from the tube head of the linear accelerator was found to be in the order of µGy, being reduced by the presence of the M2 shield. Conclusion: Using the shields showed to be an essential feature in order to reduce the dose not only on the fetus, but also in important structures responsible to its development.     

Physiologic bases of the method to increase nonspecific resistance of the organism by adaptation to intermittent normobaric hypoxia]

Impulse biorhythm of cyclic pO2 change in the uterus tissues and intrauterine fetus of rats, guinea pigs and dogs is regarded as evolution-fixed, physiological mechanism aimed at increasing nonspecific resistance of the fetus. Modeling of this mechanism by adaptation to intermittent normobaric hypoxia under impulse conditions permits more significantly increasing nonspecific resistance of the organism than application of hypoxic effect under constant conditions.     

Participation of intestinal hormones in the development of the pancreatic B-cell reactivity of rat fetuses to the action of glucose

The involvement of intestinal hormones in the development of insulin release from rat fetal pancreas was investigated. B-cell responses were determined by changes in the concentration of immunoreactive insulin after glucose addition to the incubation medium. Coincubation of fragments of fetal pancreas and duodenum from adult and newborn rats and from 21.5-day-old fetus has shown that intestinal factors can recover the response of pancreas to glucose in fetuses with experimentally removed hypothalamus and hypophysis. Besides, the intestinal factors in the fetus were found to potentiate the effect of high glucose concentrations on B cells, but had no insulinotropic effect at physiological glucose concentration in the medium. The data obtained suggest that even in the antenatal period the intestinal, along with cephalic factors, can serve as modulators of glucose action on islet B cells.