Angiotensin-converting enzyme genotype and encephalopathy in Chernobyl cleanup workers.

BACKGROUND AND PURPOSE: To identify, using a genetic model, a key role for the renin-angiotensin system (RAS) in the development of dyscirculatory encephalopathy (DE) in Chernobyl cleanup workers (CCW). The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene denotes a substantial individual variation in RAS activity with the D-allele being associated with higher ACE activity. METHODS: Ninety-three male, Caucasian CCW were recruited from those under regular review at the All-Russia Centre of Emergency and Radiation Medicine, St. Petersburg. The presence or absence of DE was determined using existing institutional guidelines. ACE genotype was determined using internationally accepted methodologies. RESULTS: Angiotensin-converting enzyme genotype distribution in 59 subjects with DE was II: 10 (17%), ID: 31 (53%), DD: 18 (30%), D-allele frequency 56.8%. Whereas in those without the condition the distribution was II: 12 (35%), ID: 19 (56%), DD 3 (9%) and D-allele frequency 35.9% (P = 0.02). CONCLUSIONS: These data are the first to identify an association between the ACE D-allele and DE in CCW. They provide evidence of a significant role for the RAS in the development of DE and suggest that clinical trials of ACE inhibition would be profitable in this group.

[Some complexities in evaluating radiation-induced mutagenic effects in man]. / O nekotorykh slozhnostiakh v otsenke radiatsionno-indutsirovannykh mutagennykh éffektov u cheloveka.

Chromosomal aberrations in somatic cells (circulating lymphocytes) have been investigated in a remote period in different groups of people who suffered from radiation accidents. The chromosomal radiation markers were found even decades after irradiation. The question about the necessity of registration of non-classical mutagenic effects after human irradiation is raised.

[Karyotypes of spontaneous human abortuses and several aspects of their phenotypic presentation]. / Kariotipy spontannykh abortusov cheloveka i nekotorye aspekty ikh fenotipicheskogo proiavleniia

In all, 172 human spontaneous abortuses were examined: 75 cases from the 1st trimester of pregnancy (all were karyotyped), and 97 ones--from 2nd and 3rd trimesters (59 cases were karyotyped). 31 cases of chromosomal anomalies were revealed. The incidence of chromosomal anomalies among the 1st and 2--3rd trimesters of spontaneous abortuses was 40.0+/-7.5 and 1.0+1.0%, resp. The general incidence of chromosomal anomalies among this series of spontaneous abortuses was equal to 18.0+/-2.9%. The question of phenotypical manifestations of chromosomal aberrations in spontaneous abortuses is discussed. The influence of gene structure of aberrant chromosomes on phenotypes of abortuses is supposed.

[Frequency of sister chromatid exchanges in human lymphocytes at different times of day]. / Chastota sestrinskikh khromatidnykh obmenov v limfotsitakh cheloveka v raznoe vremia sutok.

Analysis of the frequency of sister chromatid exchanges in the human blood taken from normal female donors was made at 9 a. m. and 9 p. m. The morning rate of exchange is shown to be less than the evening one. The influence of physiological state of the organism on the sister chromatid exchange is suggested.

[Structural and functional indices of disturbances of oocyte maturation in androgenized rats after induction of ovulation with pregnant mare's serum and luliberin]. / Strukturnye i funktsional'nye pokazateli narusheniia sozrevaniia ootsitov u androgenizirovannykh krys posle induktsii ovuliatsii syvorotkoi zhereboi kobyly i liuliberinom.

The ultrastructure of oocytes from large follicles and the meiotic maturation rate of preovulatory oocytes of intact and androgenized rats were studied. The oocytes of defeminized animals were characterized by the lack of organelles and by changes of their structure. According to the rate of meiosis they were divided into two groups. The one entered the II stage metaphase earlier than in the control, the other was characterized by a slower chromosome transformation.

[Chromosome aberrations and dominant lethals in rat oocytes during acute and chronic alcoholic intoxication]. / Khromosomnye anomalii i dominantnye letali v ootsitakh krys pri ostroi i khronicheskoi alkogol'noi intoksikatsii.

The influence of a single dose and of long-term alcohol administration on cytogenetic processes in the oocytes of Wistar white rats was studied. It is shown that a single dose of alcohol in preovulatory period when the oocytes are in the stage of diakinesismeiosis metaphase I significantly increases the rate of aneuploid gametes and dominant lethality. Analogous effect follows after long-term alcohol administration. Similarity of cytogenetic effects of acute and chronic alcohol intoxication suggests that both types of influence trigger common mechanism which results in chromosome abnormalities and, consequently, in embryonic death, i.e. dominant lethality. Taking into account that alcohol-like colchicine disturbs normal functioning of the spindle filaments, the appearance of pathology under alcohol intoxication may well be induced by disorders occurring in the stage of cell formation.

[Karyological study of human spontaneous and medical abortions]. / Kariologicheskoe issledovanie spontannykh i meditsinskikh abortov cheloveka.

PIP: 80 spontaneous abortions (40 at 6-12 weeks and 40 at 13-32 weeks of pregnancy) and 50 induced abortions (49 at 6-12 weeks and 1 at 18 weeks) were karyotyped. Among spontaneous abortions of the first trimester were found 14 different types of chromosome anomalies. The chromosome complex 48,XY, D+, F+, has not yet been described in the literature and belongs to the eempty embryonic sac 1.0:1.5 cm with a weakly developed trophoblast. Among late-term spontaneous abortions no chromosome anomalies were found. An aberrant karyotype of a 7-8 week induced abortion was revealed as 46, XX/47, XXX (5% of the nuclei with double sex chromatin and 47% with single sex chromatin). Normal karyotypes were distributed according to sex chromosome complex as follows: spontaneous abortions of 6-12 weeks, 18(XY), 8(XX); spontaneous abortions 13-32 weeks, 19(XY), 21(XX); induced abortions, 16(XY), 32(XX). The data revealed a random character in the series of investigations. The absence of the XO monosomies was noted.^ieng

[Variants of chromosome compactization and the estimation of the capacity of mammalian oocytes for further development]. / Varianty kompaktizatsii khromosom i otsenka sposobnosti ootsitov mlekopitaiushchikh k dal'neishemu razvitiiu.

The morphology of chromatin in spontaneously ovulated rat's oocytes was investigated. The degree of chromatin condensation was shown to vary widely: along with the typical cytological picture of metaphase II, both highly condensed (clamped) and decondensed ("not typical") forms of chromosomes were observed. A direct relation was discovered between the prevalence of the not typical morphological forms of oocyte chromosomes and the level of embryonal death. The shape of clamped and decondensed forms increased in the oocytes from old rats and in post-ovulatory aged oocytes.

[Chromosomal aberrations and parameters of oxidative stress in Chernobyl clean-up workers in a remote period after ionizing radiation]. / Khromosomnye aberratsii i pokazateli okislitel'nogo stressa u likvidatorov posledstvii avarii na Chernobyl'skoi AES v otdalennom periode posle deistviia ioniziruiushchei radiatsii.

This investigation was performed to test a supposition about the influence of disturbances in antioxidative system on cytogenetical parameters in Chernobyl' clean-up workers. It was shown that some cytogenetical parameters straightly correlated with the parameters of oxidative stress, while other cytogenetical parameters show just reverse correlations. Apparently, these relationships are not of cause-and-effect type, but they reflect a complex processes occurring in humans for a long period after radiation exposure.

[Interrelation of the hormonal indices and the cytologic characteristics of the germ cells]. / Vzaimosviaz' mezhdu gormonal'nymi pokazateliami i tsitologicheskoi kharakteristikoi polovykh kletok.

The analysis of the maturation of follicular oocytes as well as of the state of gametes after induction of ovulation with PMSG or with GnRH in intact and androgenized rats revealed the dependence of the heterogeneity extent (in morphologic and chromosomal damages) of population of germ cells maturing in vivo and in vitro upon the character of gonadotropin regulation disturbances of folliculogenesis. Stable disorder of reproductive function (androgenization) is followed by a significant increase in number of abnormal gametes under its hormonal correction.

[Chromosome abnormalities of human gametes and intrauterine selection. Male gametes]. / Khromosomnye anomalii gamet cheloveka i vnutriutrobnyi otbor. Issledovanie muzhskikh gamet.

Man appears to be unique among mammals with respect to very high level of reproductive wastage. It seems reasonable to suppose that many early losses attribute to cytogenetical abnormalities. However, this stage of pregnancy is difficult to be studied. The investigation of gametes is one of the most reliable ways to estimate the cytogenetical disorders in early life. The results from cytogenetical analysis of human male gametes are summarized.

[Chromosomal anomalies of human gametes and intrauterine selection. Research on female gametes]. / Khromosomnye anomalii gamet cheloveka i vnutriutrobnyi otbor. Issledovanie zhenskikh gamet.

The results of cytogenetical analysis of human oocytes are summarized. The chromosomal disorders in human gametes and in spontaneous abortions are comparatively analyzed.

[Chromosomal disorders in the oocytes of rats after stress exposure in the preovulatory period]. / Khromosomnye narusheniia v ootsitakh krys posle stressovogo vozdeistviia v preovuliatornom periode.

Female rats at the stage of proestrus have been subjected to a stress effect--immobilization for an hour. Oocytes were cytogenetically analyzed and embryonal mortality was determined. It is shown that this stress effect at the end of the fist meiotic division of the oocytes increased the rate of aneuploid gametes and the level of embryonal mortality.

[Distribution of the frequency of sister chromatid exchange among Leningrad inhabitants]. / Izuchenie raspredeleniia chastoty SKhO sredi zhitelei g. Leningrada.

Peculiarities of frequency variations in sister chromatid exchanges (SCE) were studied in a group of healthy Leningrad citizens who are not engaged in health-risk industries. No relations were found between the SCE frequency and sex, age and smoking habit (10 cigarettes per day as much). The statistical processing of the data obtained was made taking into account the errors in individual measurements of the SCE frequency. Repeated measurements revealed systematic and statistically significant variations in the rate of SCE.

Cytogenetic study of professional rescue rangers of Russian Ministry of Emergencies.

Cytogenetic studies in rescue rangers of the Russian Ministry of Emergencies has shown that this category of specialists are exposed to genotoxic factors during their professional activity. The level of induction of cytogenetic injuries of rescue team members depended on labor conditions, genotype (glutathione-S-transferase M1 and T1 xenobiotic detoxication genes), and tobacco smoking.

[Nature of the estrous cycle, incidence of anovulation, chromosome gametopathies and fetal death in female rats with 2,4-dichlorophenoxyacetic acid (2,4-D) before pregnancy]. / Kharakter éstral'nogo tsikla, chastota anovuliatsii, khromosomnye gametopatii i émbrional'naia gibel' u krys, pri zatravke samok 2,4-dokhlorfenoksiuksusnoi kislotoi (2,4-D) do beremennosti.

The effect of herbicide--2,4-D, injected before pregnancy begins, on the main parameters of the reproductive function of the female rats has demonstrated that chronic administration in doses 1 mg/kg and 12 mg/kg per day for 2 months results in certain disturbances in the estrus cycle, manifesting as prolongation of the diestrus phase and in changes of estrus and meta-estrus++ duration, as well as in an essential increase in rates of anovulatory cycles. Single administration of the preparation during the preovulatory period (50 mg/kg) produces certain disturbances in the chromosomal complex, manifesting as appearance of numerical chromosomal aberrations. When the administration is acute (10 mg/kg and 50 mg/kg) an essential increase of the embryonal death takes place, in the first case--at the expense of ++pre-implantational, and in the second--both at the expense of pre- and ++post-implantational death. At chronic administration increasing rate of the intrauterine death takes place mainly at the expense of ++post-implantational death of embryos.