Cases of the staff unaccounted exposure during the construction of the protective shell for a new confinement at the ChNPP site. / VYPADKY NEVRAKhOVANOGO OPROMINENNIa PERSONALU PRY SPORUDZhENNI ZAKhYSNOGO KONTURU NOVOGO KONFAY̆NMENTU V ZONI DSP ChAES.

OBJECTIVE: cytogenetic control of the staff radiation exposure level during the construction of the protective shell for a new confinement at the ChNPP site. MATERIALS AND METHODS: A cytogenetic examination was carried out for 32 staff persons from the contracting organ izations involved into construction of the protective shell for a new confinement. Additionally, for the goal of com parison, 28 persons who did not have professional contacts with the radiation factors were inspected. The analyti cal method of the aberrations on preparations of uniformly stained chromosomes of the peripheral blood lympho cytes has been used. The frequency has been determined for the dicentrics and centric rings with an accompanying pair fragment for 100 analyzed metaphases. The staff chronic exposure absorbed doses are estimated by means of the linear part of the linear quadratic equations, which describe the calibration dose dependence of the unstable chromosomal exchanges yield in the acute irradiated blood samples in vitro. RESULTS: Six staff persons from 32 investigated ones have the individual frequency of the recent exposure specific markers (unstable chromosomal exchanges with accompanying pair fragments) significantly higher than those for the comparison group and the population average spontaneous level. It indicates on the possibility of their exces sive irradiation during the work execution in the ChNPP zone. Single cells with two chromosomal exchanges were registered for three persons, while such cells were absent in the comparison group. This is the result of the incorpo ration of radionuclides, which are available in the air at the workplaces. The calculated averaged individual absorbed doses caused by the recent exposure of six staff persons lies in the range from 102.5 to 371.0 mGy. CONCLUSION: The doses calculated from the frequency of unstable chromosomal exchanges with the accompanying pair fragment caused by the recent exposure of six staff persons are exceeding significantly the doses determined by the methods of physical dosimetry and the occupational exposure dose limits.

[CHANGES IN THE BRAIN TESTOSTERONE METABOLISM AND SEXUAL BEHAVIOR IN MALE RATS PRENATALLY EXPOSED TO METHYLDOPA AND STRESS].

The changes of aromatase and 5α-reductase activities were studied in preoptic area (POA) and medial basal hypothalamus of 10-days-old and sexual behavior in 3-month-old male offsprings of rats exposed daily to noradrenaline antagonist methyldopa (400 mg/kg per os) 30 minutes prior to 1-hour immobilization during the last week of pregnancy (from 15th to 21st day). Prenatal stress caused aromatase activity lowering in the POA of developing brain and feminization (appearance of lordosis) and demasculinization of sexual behavior (prolongation of latent periods to the first mounting and first intromission as well as of the first ejaculation and postejaculation refractory period) in young male offspring. Oral methyldopa used prior to pregnant females stressing prevented early effect of prenatal stress on aromatase activity in the POA and normalized the male sexual behavior in young male rats by shortening both latent period to the first ejaculation and postejaculation refractory period, and an increase of numbers of ejaculation. The data obtained indicate that brain noradrenergic system plays significant role in the mechanisms of metabolic- and behavioral disturbances developing in male rats exposed to prenatal stress.

Cytogenetic indices in blood lymphocites of individuals from the staff working on new confinement buildining in Chornobyl NPP zone. / Cytogenetychni pokaznyky v limfocytah krovi grupy osib iz personalu, jakyj vykonuje roboty z budivnyctva novogo konfajnmentu v zoni ChAES.

Objective. Сytogenetic indication of possible exposure of contracting staff individuals, performing work on dismantling the ventilation pipe of "Shelter" object of Chornobyl NPP (ShO). Materials and methods. Cytogenetic examination of 12 individuals among the employees of contractors performing work on dismantling the ventilation pipe of ShO was provided. For comparison individuals who had no contact with the radiation factors for the profession activity were examined. Routine analysis method of uniformly stained chromosomes of peripheral blood lymphocytes was used. 11 388 metaphase plates were analyzed. Results. In contracting staff mean group frequency of aberrant lymphocytes, chromosome (dicentrics, acentrics, abnormal monocentrics) and chromatide type aberrations is significantly higher than such frequency in the comparison group. Three staff persons had individual frequency of specific markers of exposure - dicentric chromosomes with accompanying fragments significantly higher than their mean population level and the average frequency in the comparison group. It indicates the probability of their excess radiation when working in Chornobyl NPP local zone. Cells with two chromosome exchanges and one multiaberrant cell were registered in staff with the absence of such in control persons. The calculated estimated radiation doses of two staff persons were 87-123 mGy and and one person 210-240 mGy of acute exposure respectively. Conclusion. Calculated by frequency of dicentric chromosomes tentative "biological" doses of three staff persons show a more significant radiation effect comparing to the data of physical dosimetry.

[The dynamics of hormonal changes in female rats exposed to chronic stress and androgen excess during pubescence].

The dynamics of blood plasma corticosterone, testosterone and androstenedione levels and their reaction to acute stress (30 min immobilization) in 35-, 40- and 45-day old female rats exposed to chronic stress (daily 30-min immobilization from 35th to 45th day of life) and/or to excess of exogenous androgens (implantation of capsules with testosterone to 33-day old animals) during pubescence was studied. Both control and experimental females in all age groups responded to acute stress by significant elevation of blood plasma corticosterone levels. At the end of the chronic stress session, the extent of adrenals activation in response to acute dosed stress was lowered in androgenized 45-day old females and increased gradually in stressed ones. After acute stress, the blood plasma testosterone level decreased in control 35-day old females and rose - in androgenized females against 10-fold rising of basal hormonal level. In 40-day old control females as well as in androgenized ones exposed to chronic stress during 5 days, the acute dosed stress did not result in significant changes of blood plasma testosterone and elevated blood plasma androstenedione. Stressed 40-day old females with increased basal androstenedione secretion did not respond to acute stress by the hormone level changes while blood plasma testosterone declined significantly. At the end ofpubescence (on the 45th day of life), acute stress did not affect the blood plasma testosterone level in control and androgenized animals, while decreased it in stressed females and increased - in androgenized rats exposed to chronic stress against elevated basal level of the hormone. The conclusion is made about possible functional relationship between the changes in hormonal homeostasis during pubescence and development of reproductive system in mature animals.

[Effect of chronic stress during puberty on the reproductive system of female rats with experimental hyperandrogenicity].

Effects of chronic stress (daily 30-min immobilization) on 35-45 days of life and its combination with androgenization (implantation of testosterone-containing capsules on 33rd day of life) on reproductive system of 2.5 month old female rats were studied. The term of sexual maturation, estrous cycles regularity and structure, blood plasma levels of testosterone, progesterone and androstenedione as well as ovarian histology were examined. Androgenization resulted in the blood plasma testosterone level increase and the androstenedione level decrease, development of oligo- or anovulatory condition characterized by disorders or discontinuation in estrous cyclicity. We also detected abrupt reduction or absence of postovulatory luteal bodies, cysts formation and ovarian interstitial tissue overgrowth. All experimental animals had normal blood plasma corticosterone level. Stressed rats had no considerable changes in reproductive system except of some cyclicity disorders. Stressed against androgenization rats demonstrated delayed pubescence, an increased number of ovarian cysts along with attenuation ofandrogenization-caused negative effects on the sexual cyclicity.

[Enhancing effect of androgen receptor antagonist on gonadotropic inductors of ovulation in rats with polycystic ovaries].

Hormonal indices, phase pattern of estrous cycles, and histological structure of the ovaries were studied in female rats with polycystic ovaries caused by subcutaneous implantation of Silastic capsules with testosterone after consecutive treatment with non-steroid antiandrogen, flutamide (flutafarm), urinary FSH (menopur) and HCG (choragon). It was shown that while the plasma testosterone level was increased, administration of the drugs in subtherapeutical doses interrupted persistent diestrus, renewed estrous cycle, gonadal and uterine weights, induced appearance of postovulatory luteal bodies and restored fertility. Therefore, antiandrogen potentiation of pharmnnaco-dynamic effect of the gonadotropins with regard to their ability to ovulation induction was found out.

Prenatal dexamethasone prevents early and long-lasting neuroendocrine and behavioral effects of maternal stress on male offspring.

The hypothesis on the mediating role of hypothalamic-pituitary-adrenocortical (HPA) hormone secretion in neuroendocrine, neurochemical and behavioral alterations generated by prenatal stress in male rat offspring was tested in this study with dexamethasone (Dex) used for suppression of HIPA stress responses. Pregnant dams were being restrained daily for 1 h over the last week of gestation. In male offspring this resulted in attenuation of sex-specific pattern of the protein fractions (on the 5th postnatal day), steroid aromatase activity (on the 10th postnatal day) in the brain preoptic area, and in a decrease of male copulatory behavior, hypothalamic noradrenaline and plasma corticosterone responses to an acute stress, an increase in HPA responses to noradrenergic stimulation and other effects in adulthood. All those changes were prevented with prenatal Dex in a dose of 0.1 mg/kg b.w. injected 30 min prior to restraining pregnant dams. As such, HPA hormone secretion mediates alterations of programming of brain development induced by prenatal stress.

[The role of the ovarian steroid aromatase in pathogenesis of reproductive cycles disorders].

In the rats with regular estrous cycles effects of letrozole, a steroid aromatase inhibitor, on the enzyme activity in ovarian tissues and reproductive system condition were studied. Letrozole was administered per os daily in a dose of 1 mg/kg b.w. over 10 days. As the result of treatment, 20.5-fold decrease in aromatase activity was obtained. All animals have developed persistent anestrus with vaginal smear patterns being similar to diestrus. Uterine weights were two-fold less than that of controls, and ovarian weights increased by one third. The ovaries contained multiple cystoidal follicles. Results of the study demonstrate the key role of ovarian steroid aromatase in letrozole-induced disorders of reproductive cycles. Letrozole might be recommended for experimental modeling of reproductive cycle disorders in female rats.

[Sex characteristics of neuroendocrine effects of prenatal exposure to exogenous glucocorticoids].

The effects of hydrocortisone acetate treatment of rats during the last gestational week on neurochemical and morphological characteristics of the brain in early postnatal and mature offspring were studied. Disappearance of sexual differences both in aromatase and 5alpha-reductase activities and noradrenaline concentration in the preoptic area in 10-day old rats was found. Meanwhile a sexual dimorphism in serotonin metabolism emerged. In adult offspring, the prenatal exposure to glucocorticoids resulted in disappearance of sexual differences in neurocytes' nuclei volume in medial preoptic and suprachiasmatic nuclei. The adrenocortical reaction to noradrenaline infusion to the 3rd brain ventricle was absent in the experimental males and intensified in females. In males, adrenocortical reaction to restraint decreased while post-stress changes in hypothalamic noradrenaline concentration and hippocampal glutamate decarboxylase activity were not observed. In the similar experiments in females both the augmentation of adrenocortical reaction and inhibition of GABA-ergic system were revealed. The results obtained indicate the modifying effect of prenatal exposure to glucocorticoids on sexual dimorphism of neuroendocrine system.

Early postnatal effects of prenatal exposure to glucocorticoids on testosterone metabolism and biogenic monoamines in discrete neuroendocrine regions of the rat brain.

We investigated the effects of hydrocortisone acetate and dexamethasone administered to pregnant rats during the last gestational week on sexual differentiation of testosterone metabolism and biogenic monoamine contents and turnover in the discrete brain regions in 10-day-old offspring. In the preoptic area, sex-dependent differences in aromatase activity were attenuated by prenatal glucocorticoids. Prenatal dexamethasone but not hydrocortisone acetate caused the inversion of sexual dimorphism of 5alpha-reductase activity in the preoptic area. In the brain preoptic area of the male pups prenatally exposed to hydrocortisone acetate, a decrease in noradrenaline turnover was found. Dopamine turnover in the preoptic area and 5-hydroxytryptamine metabolism in the preoptic area and medial basal hypothalamus increased in females as a result of hydrocortisone acetate treatment. Our results indicate that excess glucocorticoids in prenatal life modifies the basic neurochemical and neurophysiological mechanisms of sexual brain differentiation and might contribute to behavioral and reproductive disorders in adulthood.

[Cytogenetic effects in blood lymphocytes of Slavutich residents having no occupational contact with ionizing radiation]. / Tsitogeneticheskie éffekty v limfotsitakh perifericheskoi krovi g. Slavutich, ne imeiushchikh professional'nogo kontakta s ioniziruiushchim izlucheniem.

A comparative cytogenetic examination of the groups of Slavutich and Kiev residents having no occupational contact with ionizing radiation was conducted. It was found a significantly higher chromosome aberration frequency in blood lymphocytes of Slavutich residents (including unstable exchanges--2.5-fold) caused by internal irradiation at the expense of local food stuff consuming. It was revealed no relationship between cytogenetic aberration frequency and initial settling time in Slavutich.

Neuroendocrine mechanisms of development of experimental hyperandrogen-induced anovulation.

An experimental model of hyperandrogen-induced anovulatory infertility (s.c. implantation of Silastic capsules containing testosterone into adult female rats) was used to study morphological, hormonal, and biochemical measures characterizing the state of the hypothalamo-hypophyseal-ovarian system. Impairments in functional androgen metabolism in the hypothalamus were seen, with decreases in the Luliberin sensitivity of the hypophysis, changes in the structure of estral cycles, and morphological changes in the ovaries; these findings are evidence for neuroendocrine disturbances in the control of ovulation. Flutamide, an experimental antiandrogen, led to partial normalization of the hormonal, biochemical, and morphological characteristics, as well as to recovery of fertility in females with anovulatory infertility.

Participation of endogenous opioids in pathogenesis of early neuroendocrine manifestations of prenatal stress syndrome.

We studied sex dimorphism in the content of norepinephrine and activity of enzymes involved in testosterone metabolism in the preoptic hypothalamic area of 10-day-old rats. Prenatal stress eliminated sex-related differences in these indices. These disturbances were absent in rats subjected to prenatal stress under conditions of opioid receptor blockade with naltrexone. These data attests to the important role of opioids in the pathogenesis of prenatal stress syndrome.

[Dynamic study of the cytogenetic effects in blood lymphocytes from humans living in the Chernobyl Atomic Energy Station exclusion zone without permission]. / Dinamicheskoe issledovanie tsitogeneticheskikh éffektov v limfotsitakh krovi liudei, nesanktsionirovanno prozhivaiuschikh v zone otchuzhdeniia Chernobyl'skoi AES.

The cytogenetic examination of a group of people, self-residing in ChNPP Exclusion Zone with soil contamination density 137Cs 74-477 kBq/m2, 90Sr 33-289 kBq/m2, 238, 239 + 240Pu 1.5-10.0 kBq/m2, was conducted in 1998-1999 and also 2001. It is shown, that after 12-15 years of the accident the level of chromosome damages in Zone self-residents' lymphocytes detected by a routine analysis is higher then at the residents of control Yagotin district, Kiev region and comes to a plateau. Lymphocytes with multiple chromosome damages are detected. The probability of its transuranium elements induction which are present in the Zone is discussed at present.

Early and long-term neuroendocrine effects of prenatal stress in male and female rats.

The effects of maternal stress, termed prenatal stress (PNS) on the neuroendocrine regulation of reproduction and the stress reactivity of offspring were studied in rats. PNS prevented the formation of sexual dimorphism in catecholamine levels, aromatase activity, and androgen 5alpha-reductase activity in the preoptic area of the brain and the mediobasal hypothalamus in 10-day-old rats. The morphological correlate of the functional lesions induced by PNS consisted of the elimination of gender-related differences in the volumes of neuron nuclei in the suprachiasmatic nucleus. Prenatal stress altered the stress and adrenergic reactivities of the hypothalamo-hypophyseal-adrenal system in mature males and females. The long-term effects of PNS were regarded as a consequence of the disruption of the hormone-neurotransmitter imprinting of the neuroendocrine system.

Prenatal stress and glucocorticoid effects on the developing gender-related brain.

Hormonal and neurotransmitter environment of nondifferentiated cells in the developing brain determines many of gender-specific behavioural and neuroendocrine functions. Early postnatal and long-term effects of maternal stress or prenatal glucocorticoid on sex-related peculiarities of the brain morphology, biogenic monoamine turnover, testosterone metabolism, hypothalamic noradrenaline (NA) and adrenocortical responses to an acute stress were studied in Wistar rat offsprings. Maternal stress (1 h immobilization daily for gestational days 15-21) prevented development of sexual dimorphism in neuronal cell nuclei volumes in suprachiazmatic nucleus (SCN) in 10 day old pups. That was associated with a disappearance of male female differences in NA and 5-hydroxytryptamine turnover in the preoptic area (POA) and dopamine (DA) turnover in the mediobasal hypothalamus (MBH) by decreasing them in male pups. Hydrocortisone acetate (5 mg daily during the last week of pregnancy) produced changes in NA turnover in the POA of males and females which were quite similar to those after maternal stress. Changes in aromatase and 5alpha-reductase activities in the POA of male pups were quite opposite as affected by maternal stress or prenatal glucocorticoid. Sexual differences in 5alpha-reductase activity in the MBH appeared due to its increase in prenatally stressed male pups. In contrast to adult males, in adult females maternal stress did not restrict hypothalamic NA and blood plasma corticosterone response to acute stress (1 h immobilization). Our findings on morphology and functions of gender-related developing brain areas stand in correlation with modifying effects of maternal stress and prenatal glucocorticoid on behavior and neuroendocrine regulations.

Endocrine mechanisms of suppressive effect of low dose estrogen-antiandrogen treatment on androgen-dependent organs of male rats.

The effects of low doses of hexestrol (Hex) (2-40 micrograms/kg bw) and flutamide (FI) (10 mg/kg bw) on some endocrine mechanisms in mature intact male rats are described in the present paper. It has been shown that each preparation, administered separately for 10 days, induced a moderate decrease in the weight of the ventral prostate (VP), anterior prostate lobe or coagulating gland (CG) and seminal vesicles (SV), in the DNA content and number of cells in the VP. 5 alpha-reductase activity was also decreased; the epithelium secretory activity of the VP was suppressed. After combined FI (10 mg/kg bw) and Hex (40 micrograms/kg bw) the following castration-like effects were observed: an abrupt fall in the weight of the accessory sexual glands, a decrease of DNA level and cell number in the VP as well as a suppression of the production of 5 alpha-reductase metabolites in this structure. Histologically, a marked degenerative changes in the VP secretory epithelium was observed; on the contrary an hyperplasia of connective and smooth muscle cells was evident. When FI alone was administered to rat, the above-mentioned changes were accompanied by a pronounced elevation of plasma bio-LH and testosterone (T) levels, also an increase of testicular delta 5-3 beta-hydroxysteroid dehydrogenase activity was observed. On the contrary, when Hex was administered alone or in combination with FI, bio-LH and T levels and enzyme activity decreased. We conclude that Hex administration in low doses, in combination with FI, could be an alternative method for a complete androgen blockade of the accessory sexual glands.

[The effect of prenatal stress on the development of hypophyseal gonadotropic function in male rats]. / Vliianie prenatal'nogo stressa na stanovlenie gonadotropnoi funktsii gipofiza u samtsov krys.

Significant changes of the aromatase and 5 alpha-reductase hypothalamic activity were found in juvenile prenatally stressed male Wistar rats. The blood plasma testosterone level increased following niftolide (NF) or 1, 4, 6-androstatine-3, 17-dione (ATD) administration. Prenatal stress seems to exert a modifying effect upon the regulating mechanisms of the pituitary gonadotropin function, lowering the functional reserves of the hypothalamo-hypophyseal-testicular axis in pre- and postpubertal male rats.

[Recovery of various parameters of the functional state of the reproductive system in thymectomized rats as affected by thymic membrane factor]. / Vosstanovlenie nekotorykh pokazatelei funktsional'nogo sostoianiia reproduktivnoi sistemy u timéktomirovannykh krys pod vliianiem membrannogo faktora timusa.

Ten-month-old male rats thymectomized in early post-puberty were ascertained to have lower plasma luteinizing and testicular hormones and higher testicular steroid dehydrogenase activity. Following 24 hours of administration of a thymocyte membrane structural agent, pituitary gonadotropic and gonadal androgenic functions became normal. There was no agreement between the hormonal parameters and the levels of nucleic acids in the testes and prostate.

[The neuroendocrine mechanisms of the development of the anovulatory hyperandrogenic syndrome in rats]. / Neiroendokrynni mekhanizmy rozvytku anovuliatornoho syndromu hiperandrohennoho pokhodzhennia u shchuriv.

The anovulatory syndrome in adult female rats occurred after subcutaneous implantation of silastic capsules with testosterone. Acceleration of testosterone conversion into estradiol in the hypothalamus, suppression of pituitary LH responsiveness to LHRH, increase of blood plasma bioactive LH, estrous cycle disorder as well as morphological changes in ovaries demonstrate the alterations in neuroendocrine control of ovulation.