Multiparametric radiobiological assays show that variation of X-ray energy strongly impacts relative biological effectiveness: comparison between 220 kV and 4 MV.

Based on classic clonogenic assay, it is accepted by the scientific community that, whatever the energy, the relative biological effectiveness of X-rays is equal to 1. However, although X-ray beams are widely used in diagnosis, interventional medicine and radiotherapy, comparisons of their energies are scarce. We therefore assessed in vitro the effects of low- and high-energy X-rays using Human umbilical vein endothelial cells (HUVECs) by performing clonogenic assay, measuring viability/mortality, counting γ-H2AX foci, studying cell proliferation and cellular senescence by flow cytometry and by performing gene analysis on custom arrays. Taken together, excepted for γ-H2AX foci counts, these experiments systematically show more adverse effects of high energy X-rays, while the relative biological effectiveness of photons is around 1, whatever the quality of the X-ray beam. These results strongly suggest that multiparametric analysis should be considered in support of clonogenic assay.

Genetic modifiers of radon-induced lung cancer risk: a genome-wide interaction study in former uranium miners.

PURPOSE: Radon is a risk factor for lung cancer and uranium miners are more exposed than the general population. A genome-wide interaction analysis was carried out to identify genomic loci, genes or gene sets that modify the susceptibility to lung cancer given occupational exposure to the radioactive gas radon. METHODS: Samples from 28 studies provided by the International Lung Cancer Consortium were pooled with samples of former uranium miners collected by the German Federal Office of Radiation Protection. In total, 15,077 cases and 13,522 controls, all of European ancestries, comprising 463 uranium miners were compared. The DNA of all participants was genotyped with the OncoArray. We fitted single-marker and in multi-marker models and performed an exploratory gene-set analysis to detect cumulative enrichment of significance in sets of genes. RESULTS: We discovered a genome-wide significant interaction of the marker rs12440014 within the gene CHRNB4 (OR = 0.26, 95% CI 0.11-0.60, p = 0.0386 corrected for multiple testing). At least suggestive significant interaction of linkage disequilibrium blocks was observed at the chromosomal regions 18q21.23 (p = 1.2 × 10-6), 5q23.2 (p = 2.5 × 10-6), 1q21.3 (p = 3.2 × 10-6), 10p13 (p = 1.3 × 10-5) and 12p12.1 (p = 7.1 × 10-5). Genes belonging to the Gene Ontology term "DNA dealkylation involved in DNA repair" (GO:0006307; p = 0.0139) or the gene family HGNC:476 "microRNAs" (p = 0.0159) were enriched with LD-blockwise significance. CONCLUSION: The well-established association of the genomic region 15q25 to lung cancer might be influenced by exposure to radon among uranium miners. Furthermore, lung cancer susceptibility is related to the functional capability of DNA damage signaling via ubiquitination processes and repair of radiation-induced double-strand breaks by the single-strand annealing mechanism.

Inclusion of dosimetric data as covariates in toxicity-related radiogenomic studies : A systematic review.

PURPOSE: This systematic review evaluates the completeness of dosimetric features and their inclusion as covariates in genetic-toxicity association studies. MATERIALS AND METHODS: Original research studies associating genetic features and normal tissue complications following radiotherapy were identified from PubMed. The use of dosimetric data was determined by mining the statement of prescription dose, dose fractionation, target volume selection or arrangement and dose distribution. The consideration of the dosimetric data as covariates was based on the statement mentioned in the statistical analysis section. The significance of these covariates was extracted from the results section. Descriptive analyses were performed to determine their completeness and inclusion as covariates. RESULTS: A total of 174 studies were found to satisfy the inclusion criteria. Studies published ≥2010 showed increased use of dose distribution information (p = 0.07). 33% of studies did not include any dose features in the analysis of gene-toxicity associations. Only 29% included dose distribution features as covariates and reported the results. 59% of studies which included dose distribution features found significant associations to toxicity. CONCLUSION: A large proportion of studies on the correlation of genetic markers with radiotherapy-related side effects considered no dosimetric parameters. Significance of dose distribution features was found in more than half of the studies including these features, emphasizing their importance. Completeness of radiation-specific clinical data may have increased in recent years which may improve gene-toxicity association studies.

A cytogenetic study of hospital workers occupationally exposed to radionuclides in Serbia: premature centromere division as novel biomarker of exposure?

PURPOSE: The health risk of chronic exposure to radionuclides includes changes in the genome (e.g., chromosomal aberrations and micronuclei) that increase chromosomal instability. There are also other phenomena, which seem to appear more frequently in metaphases of exposed persons (such as premature centromere division). The aim of this study was to discover whether or not there is correlation between incidence of named cytogenetic changes in persons occupationally exposed to radionuclides in comparison with unexposed control group, and if significant correlation is determined, can premature centromere division be consider as a biomarker of radiation exposure? METHODS: The exposed group comprised 50 individuals occupationally exposed to radionuclides. The reference control group consisted of 40 unexposed individuals. Chromosomal aberrations, micronuclei and premature centromere division were analyzed according to a standard International Atomic Energy Agency protocol. Statistical analyses were performed using SPSS 17.0 statistics. RESULTS: The means for analyzed cytogenetic changes were significantly higher in the exposed group. Positive correlation between them was found in exposed group. Premature centromere division parameter PCD5-10 was selected as particularly suitable for separating groups (exposed/unexposed). CONCLUSIONS: Identification of other phenomena related to radionuclide exposure, beside well known, may clarify recent problems in radiobiology concerning the biological response to low doses of ionizing radiation and its consequences.

Toward the development of transcriptional biodosimetry for the identification of irradiated individuals and assessment of absorbed radiation dose.

The most frequently used and the best established method of biological dosimetry at present is the dicentric chromosome assay, which is poorly suitable for a mass casualties scenario. This gives rise to the need for the development of new, high-throughput assays for rapid identification of the subjects exposed to ionizing radiation. In the present study, we tested the usefulness of gene expression analysis in blood cells for biological dosimetry. Human peripheral blood from three healthy donors was X-irradiated with doses of 0 (control), 0.6, and 2 Gy. The mRNA level of 16 genes (ATF3, BAX, BBC3, BCL2, CDKN1A, DDB2, FDXR, GADD45A, GDF15, MDM2, PLK3, SERPINE1, SESN2, TNFRSF10B, TNFSF4, and VWCE) was assessed by reverse transcription quantitative PCR 6, 12, 24, and 48 h after exposure with ITFG1 and DPM1 used as a reference genes. The panel of radiation-responsive genes was selected comprising GADD45A, CDKN1A, BAX, BBC3, DDB2, TNFSF4, GDF15, and FDXR. Cluster analysis showed that ΔC t values of the selected genes contained sufficient information to allow discrimination between irradiated and non-irradiated blood samples. The samples were clearly grouped according to the absorbed doses of radiation and not to the time interval after irradiation or to the blood donor.

Quantifying murine bone marrow and blood radiation dose response following (18)F-FDG PET with DNA damage biomarkers.

The purpose of this study was to quantify the poorly understood radiation doses to murine bone marrow and blood from whole-body fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET), by using specific biomarkers and comparing with whole body external low dose exposures. Groups of 3-5 mice were randomly assigned to 10 groups, each receiving either a different activity of (18)F-FDG: 0-37MBq or whole body irradiated with corresponding doses of 0-300mGy X-rays. Blood samples were collected at 24h and at 43h for reticulocyte micronucleus assays and QPCR analysis of gene expression in peripheral blood leukocytes. Blood and bone marrow dose estimates were calculated from injected activities of (18)F-FDG and were based on a recommended ICRP model. Doses to the bone marrow corresponding to 33.43mGy and above for internal (18)F-FDG exposure and to 25mGy and above for external X-ray exposure, showed significant increases in radiation-induced MN-RET formation relative to controls (P<0.05). Regression analysis showed that both types of exposure produced a linear response with linear regression analysis giving R(2) of 0.992 and 0.999 for respectively internal and external exposure. No significant difference between the two data sets was found with a P-value of 0.493. In vivo gene expression dose-responses at 24h for Bbc3 and Cdkn1 were similar for (18)F-FDG and X-ray exposures, with significant modifications occurring for doses over 300mGy for Bbc3 and at the lower dose of 150mGy for Cdkn1a. Both leucocyte gene expression and quantification of MN-RET are highly sensitive biomarkers for reliable estimation of the low doses delivered in vivo to, respectively, blood and bone marrow, following (18)F-FDG PET.

The identification of candidate radio marker genes using a coexpression network analysis in gamma-irradiated rice.

Plant physiological and biochemical processes are significantly affected by gamma irradiation stress. In addition, gamma-ray (GA) differentially affects gene expression across the whole genome. In this study, we identified radio marker genes (RMGs) responding only to GA stress compared with six abiotic stresses (chilling, cold, anoxia, heat, drought and salt) in rice. To analyze the expression patterns of differentially expressed genes (DEGs) in gamma-irradiated rice plants against six abiotic stresses, we conducted a hierarchical clustering analysis by using a complete linkage algorithm. The up- and downregulated DEGs were observed against six abiotic stresses in three and four clusters among a total of 31 clusters, respectively. The common gene ontology functions of upregulated DEGs in clusters 9 and 19 are associated with oxidative stress. In a Pearson's correlation coefficient analysis, GA stress showed highly negative correlation with salt stress. On the basis of specific data about the upregulated DEGs, we identified the 40 candidate RMGs that are induced by gamma irradiation. These candidate RMGs, except two genes, were more highly induced in rice roots than in other tissues. In addition, we obtained other 38 root-induced genes by using a coexpression network analysis of the specific upregulated candidate RMGs in an ARACNE algorithm. Among these genes, we selected 16 RMGs and 11 genes coexpressed with three RMGs to validate coexpression network results. RT-PCR assay confirmed that these genes were highly upregulated in GA treatment. All 76 genes (38 root-induced genes and 38 candidate RMGs) might be useful for the detection of GA sensitivity in rice roots.

Integrated analysis of diverse transcriptomic data from Arabidopsis reveals genetic markers that reliably and reproducibly respond to ionizing radiation.

Studies focused on the responses of plants to ionizing radiation are becoming more important due to the increased need for radiation-induced mutations, post-harvest or phytosanitary irradiation treatment of plants, and environmental monitoring of radioactive sites. To elucidate the influence of ionizing radiation on genome-wide transcription in plants, we performed integrated analysis of diverse transcriptomic data from different Arabidopsis samples and at various time points after γ irradiation or H2O2 treatment. The expression levels of most of the differentially expressed genes (DEGs) that were induced or repressed after γ irradiation returned to baseline levels of transcription within 12h, while some of these genes showed prolonged transcriptional changes. Expression of the DEGs did not correlate with genomic DNA methylation; however, there were substantial differences in DEG levels between the wild type and the cmt3-11 mutant, which has a defect in non-CG DNA methylation. Moreover, the proportion of the DEGs in common between 2 independent experiments using different batches of samples was only 12-18%. These results suggest that there is a diversity or randomness in radiation-induced physiological or phenotypic alterations. However, the results also indicated that 47 DEGs maintained a transcriptional change until 48h, and 7 of them, until 16d. Forty-five additional DEGs were found to be sustainably induced or repressed until 24h after γ irradiation regardless of sample-to-sample variation or genotype, and 4 or 2 of them, until 5d or 16d, respectively. Therefore, we suggest that the 4 γ-ray-responsive genes that showed sustainable transcriptional changes until day 5 would be reliable and reproducible genetic markers when evaluating the responsiveness of plants to γ-rays.

Visualización de la anatomía fetal por ecografía prenatal entre las semanas 11-13+6 / Visualising foetal anatomy by prenatal ultrasound between weeks 11-13+6

Objetivo. Comunicar la capacidad de visualización de estructuras anatómicas fetales durante la ecografía habitual de valoración de marcadores entre las semanas 11 y 13+6 de gestación en la Unidad de Ecografía del Centro Gutenberg de Málaga. Métodos. Evaluamos 990 pacientes que consultaron para valoración del cálculo de riesgo para trisomía 21, de las cuales 652 fueron utilizadas para el análisis. En 20 minutos realizamos la evaluación del grosor de la translucencia nucal y marcadores ecográficos adicionales, además de intentar valorar las principales estructuras anatómicas fetales, incluido el corazón, por vía abdominal o transvaginal según preferencia del operador. Resultados. El índice de masa corporal materno medio fue de 23,9; la media de la edad gestacional fue de 12 semanas; la longitud craneocaudal media fue de 62,6mm y la translucencia nucal se consideró por encima del percentil 95 en el 8,6% de los casos. Obtuvimos más del 90% de visualización (normal o con malformación) de cabeza y cerebro, cara, cuello, tórax, abdomen, extremidades y columna. Sin embargo, el corazón y los riñones ofrecieron mayor dificultad con una identificación global del 76 y 67% respectivamente. La mayoría del las exploraciones se realizaron con abordaje abdominal. Conclusiones. Es posible visualizar la anatomía fetal en más del 90% de los fetos, con más facilidad y éxito en la semana 13. La valoración del corazón y los riñones presentó siempre más dificultades. Destacamos la importancia de evaluar la anatomía fetal junto a los marcadores de aneuploidía en las semanas 11-13+6(AU)

Objective. To report the feasibility of identifying the foetal anatomy during the routine 11 to 13+6 weeks scan in the Ultrasound Unit at the Gutenberg Centre in Malaga, Spain. Methods. We examined 990 patients who attended our Unit to carry out the ultrasound screening for chromosomal abnormalities and risk assessment for trisomy 21, and 652 were included for the analysis. We measured the nuchal translucency thickness and additional ultrasound markers during the 20minutes allocated. In addition, we tried to visualise the main foetal anatomic structures, including the heart. The scans were done abdominally or by transvaginal approach, according to the preference of the operator. Results. The mean maternal body mass index was 23.9 and the mean gestation was 12 weeks; the mean crown rump length was 62.6mm and the nuchal translucency thickness was above the 95th centile for gestation in 8.6% of the foetuses. Visualisation of the foetal anatomy was successful in 90% of cases, classified as normal or abnormal, in most of the structures. However, the heart and kidneys were more difficult to identify with confidence and success was achieved in 76% and 67%, respectively. The large majority (93%) of the scans were performed abdominally. Conclusions. It is feasible to visualise the foetal anatomy in more than 90% of the cases during the routine first trimester scan. The heart and the kidneys remained the most difficult. We would like to stress the importance of the anatomical survey in the 11 to 13+6 weeks scan, in addition to the ultrasound markers assessment for the screening of chromosomal defects(AU)

[The alterations in profiles of RAPD- and of ISSR-markers in progeny of the single gamma-irradiated mice of BALB/c strain].

Molecular-genetic effects in the offspring of BALB/c male mice exposed to single radiation doses of 1, 2 and 3 Gy were studied. Induced genetic variability was studied using such methods as assessment of variation RAPD- and ISSR-profiles. Comparative analysis of genetic radiosensitivity of stem spermatogonia and of spermatids is presented in the work. The frequency of changes in the patterns of the offsprings of irradiated mice was significantly different from the analogous parameters in the offsprings of the control group already at a dose of 1 Gy. Comparative analysis of genetic radiosensitivity at different stages of spermatogenesis revealed the similar sensitivity of spermatogonia and of spermatids at 1 and 3 Gy and a higer sensitivity of spematogonia at 2 Gy.

[Distribution of genetic markers in offsprings of irradiated individuals].

For the estimation of radiation exposure on genetic processes in Mayak PA population we studied the distribution of a number of genetic markers in offsprings of Mayak PA workers depending on radiation (preconceptive and antenatal chronic exteral gamma-radiation) and non-radiation (age-sex characteristics of children and age characteristics of parents to the moment of conception) factors. Relatively unfavorable changes in distribution of genotypes and genes of haptoglobin genetic system in offsprings, whose parents (one or both) were exposed to external gamma-radiation in preconceptive cumulative dose of more than 200 cGy were detected. The most obvious reason of such changes may consist in directed gametic selection (Hp2 allele versus Hp1 allele) which turns out in abnormalities of segregation of Hp2-1 heterozygote that have both alleles. Effect of antenatal exposure on distribution of studied genetic markers in offspring of exposed population in studied dose range were not found. Homotypic changes in distribution of ABO bood groups and alleles in offspring of exposed and unexposed individuals depending on age characteristics of parents (middle age and age differences of both parents) for the moment of conception were also detected.

Identification of ultraviolet B-sensitive genes in human peripheral blood cells.

Ultraviolet B (UVB) is a serious irritant for the skin and increases a risk for skin cancer. To identify UVB-sensitive genes in peripheral blood, 11 healthy male volunteers were exposed to 0.3 J/cm(2) of narrow-band (NB)-UVB, about half of minimal erythema dose (MED) in Japanese, and gene expression in blood was analyzed at 4 h, 24 h, 4 d and 7 d after the irradiation using microarray carrying oligonucleotide probes for 2,000 stress-responsive genes. RNA prepared before the irradiation was used as a reference control. Microarray analysis identified 21 genes as UVB-responsive genes with a peak at 24 h in 6 subjects, and real-time PCR validated the significant down-regulation of 9 (ABCB10, ATF1, ABCD3, TANK, FAS, SLC30A9, CHUK, CASP1, and ABCE1) out of the 21 genes in 11 subjects. Considering sensitive and characteristic features of 9 marker genes, they may be useful indicators for monitoring systemic response to UVB irradiation.

Single extreme low dose/low dose rate irradiation causes alteration in lifespan and genome instability in primary human cells.

To investigate the long-term biological effect of extreme low dose ionising radiation, we irradiated normal human fibroblasts (HFLIII) with carbon ions (290 MeV u(-1), 70 keV microm(-1)) and gamma-rays at 1 mGy (total dose) once at a low dose rate (1 mGy 6-8 h(-1)), and observed the cell growth kinetics up to 5 months by continuous culturing. The growth of carbon-irradiated cells started to slow down considerably sooner than that of non-irradiated cells before reaching senescence. In contrast, cells irradiated with gamma-rays under similar conditions did not show significant deviation from the non-irradiated cells. A DNA double strand break (DSB) marker, gamma-H2AX foci, and a DSB repair marker, phosphorylated DNA-PKcs foci, increased in number when non-irradiated cells reached several passages before senescence. A single low dose/low dose rate carbon ion exposure further raised the numbers of these markers. Furthermore, the numbers of foci for these two markers were significantly reduced after the cells became fully senescent. Our results indicate that high linear energy transfer (LET) radiation (carbon ions) causes different effects than low LET radiation (gamma-rays) even at very low doses and that a single low dose of heavy ion irradiation can affect the stability of the genome many generations after irradiation.

[The influence of chronic and of acute irradiation on the polymorphism of RAPD-markers in offspring for irradiated mice].

On mice lines BALB/c and CBA/lac was performed the study of molecular-genetics effects in mice progeny after the chronic (dose rate -0.0017 Gy/day, total dose -0.36 Gy) and acute (dose range 1-3 Gy) exposure of y-radiation on the parents. For variability analysis was used technique of amplification DNA with series of random primers (RAPD-assay). Random primers were used as single primer and in mixture of ones. In this work were held the comparative analysis of the genetic radiosensitivity for stem spermatogonia and spermatides. After the acute exposure the dose dependence for levels of polymorphism of RAPD-markers were obtained. After the chronic irradiation, significant differences from control group were obtained only by use primers mixture M1. Comparative analysis of the genetic radiosensitivity of different stages of mice spermatogenesis are display is similar sensitivity of stem spermatogonia and spermatides after doses of irradiation 1 Gy and 3 Gy. Indicated that after irradiation by dose 2 Gy, spermatogonia are more sensitivity than spermatides.

Stable intrachromosomal biomarkers of past exposure to densely ionizing radiation in several chromosomes of exposed individuals.

A multicolor banding (mBAND) fluorescence in situ hybridization technique was used to investigate the presence inhuman populations of a stable biomarker-intrachromosomal chromosome aberrations-of past exposure to high-LET radiation. Peripheral blood lymphocytes were taken from healthy Russian nuclear workers occupationally exposed from 1949 onward to either plutonium, gamma rays or both. Metaphase spreads were produced and chromosomes 1 and 2 were hybridized with mBAND FISH probes and scored for intra-chromosomal aberrations. A large yield of intrachromosomal aberrations was observed in both chromosomes of the individuals exposed to high doses of plutonium, whereas there was no significant increase over the (low) background control rate in the population who were exposed to high doses of gamma rays. Interchromosome aberration yields were similar in both the high plutonium and the high gamma-ray groups. These results for chromosome 1 and 2 confirm and extend data published previously for chromosome 5. Intrachromosomal aberrations thus represent a potential biomarker for past exposure to high-LET radiations such as alpha particles and neutrons and could possibly be used as a biodosimeter to estimate both the dose and type of radiation exposure in previously exposed populations.

The first-generation whole-genome radiation hybrid map in the horse identifies conserved segments in human and mouse genomes.

A first-generation radiation hybrid (RH) map of the equine (Equus caballus) genome was assembled using 92 horse x hamster hybrid cell lines and 730 equine markers. The map is the first comprehensive framework map of the horse that (1) incorporates type I as well as type II markers, (2) integrates synteny, cytogenetic, and meiotic maps into a consensus map, and (3) provides the most detailed genome-wide information to date on the organization and comparative status of the equine genome. The 730 loci (258 type I and 472 type II) included in the final map are clustered in 101 RH groups distributed over all equine autosomes and the X chromosome. The overall marker retention frequency in the panel is approximately 21%, and the possibility of adding any new marker to the map is approximately 90%. On average, the mapped markers are distributed every 19 cR (4 Mb) of the equine genome--a significant improvement in resolution over previous maps. With 69 new FISH assignments, a total of 253 cytogenetically mapped loci physically anchor the RH map to various chromosomal segments. Synteny assignments of 39 gene loci complemented the RH mapping of 27 genes. The results added 12 new loci to the horse gene map. Lastly, comparison of the assembly of 447 equine genes (256 linearly ordered RH-mapped and additional 191 FISH-mapped) with the location of draft sequences of their human and mouse orthologs provides the most extensive horse-human and horse-mouse comparative map to date. We expect that the foundation established through this map will significantly facilitate rapid targeted expansion of the horse gene map and consequently, mapping and positional cloning of genes governing traits significant to the equine industry.

Lack of mutation induction with exposure to 1.5 GHz electromagnetic near fields used for cellular phones in brains of Big Blue mice.

The possible mutagenic potential of exposure to 1.5 GHz electromagnetic near field (EMF) was investigated using brain tissues of Big Blue mice (BBM). Male BBM were locally exposed to EMF in the head region at 2.0, 0.67, and 0 W/kg specific absorption rate for 90 min/day, 5 days/week, for 4 weeks. No gliosis or degenerative lesions were histopathologically noted in brain tissues, and no obvious differences in Ki-67 labeling and apoptotic indices of glial cells were evident among the groups. There was no significant variation in the frequency of independent mutations of the lacI transgene in the brains. G:C to A:T transitions at CpG sites constituted the most prevalent mutations in all groups and at all time points. Deletion mutations were slightly increased in both the high and low EMF exposure groups as compared with the sham-exposed group, but the differences were not statistically significant. These findings suggest that exposure to 1.5 GHz EMF is not mutagenic to mouse brain cells and does not create any increased hazard with regard to brain tumor development.

Analysis of loss of heterozygosity in lymphoma and leukaemia arising in F1 hybrid mice locates a common region of chromosome 4 loss.

Previous studies have identified five lymphoma-related tumour suppressor gene regions on murine chromosome 4. Using detailed allelotype analysis on a range of lympho-haematopoietic tumour types arising in F1 hybrid mice, we now show a consistent pattern of loss of heterozygosity (LOH) which identifies a common region of loss delineated by microsatellites D4Mit21 and D4Mit53 on proximal chromosome 4. This critical segment corresponds to the thymic lymphoma tumour suppressor region 5 (TLSR5) identified in an earlier study. Tumours of this type have also been reported as showing allelic loss from the Trp53 and Ikaros regions on chromosome 11. In the present study, only a small fraction of tumours showed LOH in the Ikaros region, while a minority of lymphomas, but not acute myeloid leukaemias, showed allelic loss of the chromosome 11 segment encoding Trp53. These and other data indicate strongly that the genomic regions identified as showing recurrent LOH depend on the genetic background of the mice. Overall, the results indicate a key role for a tumour suppressor gene(s) encoded in an approximately 3 cM segment on proximal chromosome 4 and provide an experimental basis for the further investigation of the functional role of candidate genes which include Pax5 and Tgfbr1.

Telomeric associations in cigarette smokers exposed to low levels of X-rays.

Telomeric association (TA), i.e. fusion of chromosomes by their telomeres, predisposes a cell to genetic instability. Because of this we investigated the effect of X-rays exposure and cigarette smoking on the frequency of TA in peripheral blood lymphocytes of exposed individuals, in order to determine if TA can be a chromosomal marker in populations exposed to these carcinogens and if there is an synergistic effect between both agents. We found that the exposed groups show a greater percentage of TA when compared with the control group (P<0.001). However, although the percentage of metaphases with TA in the group with combined exposure (12.6%) was greater than in the others exposed groups (P<0.05), this value was less than the sum of the two individual effects (15.1%). Our results suggest that probably there is not an additive or synergistic effect between X-rays and smoking, and that TA may be a useful cytogenetic marker for evaluating populations exposed to mutagens.

[Nuclei with protrusions--"tailed" nuclei--and radiation cytogenetic markers in a lymphocyte culture after x-ray irradiation]. / Iadra s protruziiami--"khvostatye" iadra i radiatsionnye tsitogeneticheskie markery v kul'ture limfotsitov posle rentgenovskogo oblucheniia.

Frequency of the appearance of binuclear cells with nuclei having outgrowth into the cytoplasmic space and arise after first mitosis in human lymphocyte culture is linear-square dependent on the X-irradiation at doses from 0.0 to 4.0 Gy. Positive correlation between frequency of cells with "tailed" nuclei and frequency of metaphases of first mitosis having dicentrics and rings was established. Apparently, formation such "tailed" nuclei is connected with dicentrics and rings.