Spontaneous Chromosome Aberrations Research Articles

Abstract IA014: BRCA2 promotes genomic integrity and therapy resistance primarily through its role in homology-directed repair

Abstract Tumor suppressor BRCA2 functions in multiple pathways. The role of BRCA2 in homologous recombination, also termed homology-directed repair (HDR), is particularly well known. We also showed that it has a key role in the protection of stalled replication forks from the MRE11 nuclease. Moreover, BRCA2 also suppresses the formation of single-stranded gaps during replication. We have attempted to delineate the relative contributions of these three pathways to the maintenance of genome integrity and chemotherapy response using separation of function alleles. First, we report that mouse and human cells require a RAD51 filament stabilization motif in BRCA2 for both fork protection and gap suppression but not HDR. In mice, loss of fork protection and gap suppression do not compromise genome instability or shorten tumor latency. By contrast, HDR deficiency increases spontaneous and replication stress-induced chromosome aberrations and tumor predisposition. Unlike with HDR, fork protection and gap suppression defects are also observed in Brca2 heterozygous cells from mice, likely due to reduced RAD51 stabilization at stalled forks and gaps. Sensitivity to the PARP inhibitor olaparib is greatest for HDR-deficient cells, although fork protection/gap suppression-defective cells show a weak sensitivity. Gaps arise from PRIMPOL activity, which is associated with sensitivity to 5-hydroxymethyl-2’-deoxyuridine (hmdU) and DNPH1 inhibition due to the formation of SMUG1-generated abasic sites and is exacerbated by poly(ADP-ribose) polymerase inhibition. In summary, this work demonstrates that HDR deficiency has the major role in generating sensitivity to chemotherapeutics, although gap suppression deficiency may be targeted by specific agents. Citation Format: Pei Xin Lim, Maria Jasin. BRCA2 promotes genomic integrity and therapy resistance primarily through its role in homology-directed repair [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr IA014.

BRCA2 promotes genomic integrity and therapy resistance primarily through its role in homology-directed repair

Tumor suppressor BRCA2 functions in homology-directed repair (HDR), the protection of stalled replication forks, and the suppression of replicative gaps, but their relative contributions to genome integrity and chemotherapy response are under scrutiny. Here, we report that mouse and human cells require a RAD51 filament stabilization motif in BRCA2 for fork protection and gap suppression but not HDR. In mice, the loss of fork protection/gap suppression does not compromise genome stability or shorten tumor latency. By contrast, HDR deficiency increases spontaneous and replication stress-induced chromosome aberrations and tumor predisposition. Unlike with HDR, fork protection/gap suppression defects are also observed in Brca2 heterozygous cells, likely due to reduced RAD51 stabilization at stalled forks/gaps. Gaps arise from PRIMPOL activity, which is associated with 5-hydroxymethyl-2'-deoxyuridine sensitivity due to the formation of SMUG1-generated abasic sites and is exacerbated by poly(ADP-ribose) polymerase (PARP) inhibition. However, HDR proficiency has the major role in mitigating sensitivity to chemotherapeutics, including PARP inhibitors.

A retrospective analysis of spontaneous chromosomal aberrations in human lymphocyte cultures of individuals from Bosnia and Herzegovina

Spontaneous chromosomal aberrations are structural or numerical changes of chromosomes that occur naturally, without exposure to external genotoxic factors. They are not inherited, occur randomly in the karyotype, and do not have direct clinical significance. However, they can affect genomic instability and disease predisposition. They can result from DNA replication or repair processes errors, and typically are observed in cells that are actively dividing. Spontaneous chromosomal aberrations may arise due to the natural chromosomal instability and can be elevated in individuals exposed to mutagens. We analyzed frequencies of spontaneous chromosomal aberrations in 137 individuals subjected to karyotype analysis at the Laboratory for Cytogenetics and Genotoxicology, University of Sarajevo – Institute for Genetic Engineering and Biotechnology, during 2008-2023. Whole blood samples were cultivated for 72 hours with the thymidine added in the 48th hour. Metaphases were arrested by colcemid 60 minutes before harvesting. GTG banding was performed and slides were analyzed under 1000x magnification in accordance with An International System for Human Cytogenetic Nomenclature and E.C.A. Cytogenetic Guidelines and Quality Assurance. Constitutionally aberrant karyotypes were found in 2.92% of analysed individuals as well as altered karyotypes considered as normal chromosomal variants. In the total of 3092 analyzed metaphases, 20 spontaneous chromosomal aberrations were found in 13 individuals. This study contributes to the limited knowledge of the cytogenetic status of the Bosnian and Herzegovinian population. Further monitoring of spontaneous chromosomal aberrations incidences is recommended.

Chromosomal breakage tests in the differential diagnosis of Fanconi anemia and aplastic anemia.

FA patients are hypersensitive to preconditioning of bone marrow transplantation. Assessment of the power of mitomycin C (MMC) test to assign FA patients. We analysed 195 patients with hematological disorders using spontaneous and two types of chromosomal breakage tests (MMC and bleomycin). In case of presumed Ataxia telangiectasia (AT), patients' blood was irradiated in vitro to determine the radiosensitivity of the patients. Seven patients were diagnosed as having FA. The number of spontaneous chromosomal aberrations was significantly higher in FA patients than in aplastic anemia (AA) patients including chromatid breaks, exchanges, total aberrations, aberrant cells. MMC-induced ≥10 break/cell was 83.9 ± 11.4% in FA patients and 1.94 ± 0.41% in AA patients (p < .0001). The difference in bleomycin-induced breaks/cell was also significant: 2.01 ± 0.25 (FA) versus 1.30 ± 0.10 (AA) (p = .019). Seven patients showed increased radiation sensitivity. Both dicentric + ring, and total aberrations were significantly higher at 3 and 6 Gy compared to controls. MMC and Bleomycin tests together proved to be more informative than MMC test alone for the diagnostic classification of AA patients, while in vitro irradiation tests could help detect radiosensitive-as such, individuals with AT.

Abstract A045: Examining the role of RNA:DNA hybrids (r loops) in glioblastoma multiforme cell motility and invasion

Abstract Glioblastoma multiforme (GBM) is a highly aggressive brain cancer. The standard course of treatment is a combination of radiation and chemotherapy. Even with the dual treatment, the 5-year survival rate of patients with GBM is between 4-10%. A possible cause of the low survival rate for GBM patients is the presence of motile neoplastic cells with efficient DNA repair abilities. Thus, the two major obstacles to treating GBMs is 1) the tumors inherent invasive nature and 2) the recurrent tumors ability to acquire treatment resistance. As such, gaining a better understanding of the mechanisms mediating GBM recurrence would allow us to design better treatment strategies for patients. We have found that the 5’-3’ exoribonuclease XRN2 is upregulated in GBMs as compared to normal and other brain cancer types. While XRN2 is traditionally associated with the process of transcription termination, our published work has defined a role for XRN2 in the DNA damage response. Our group has shown that loss of XRN2 sensitizes to a variety of DNA damaging agents but in particular ionizing radiation. Previously, we have shown that XRN2 is required for DNA repair, specifically double stranded break (DSB) repair. Loss of XRN2 impairs both the non-homologous end-joining and homologous recombination DSB repair pathways. Loss of XRN2 also results in increased spontaneous DSB formation, chromosomal aberrations and RNA:DNA hybrid (R-loop) formation. In addition to a role in the DNA damage response, we found that loss of XRN2 is required for GBM cell motility, invasion through a matrix and decreased tumor volume in mouse models. Interestingly, R-loop formation can affect gene expression by modulating the access of genes to transcription factors, miRNA transcription, and methylation status of genes. To gain a better understanding of how XRN2 modulates gene expression, we conducted RNA-Seq analyses of GBM cell lines with and without XRN2 expression and found that XRN2 can regulate genes involved in cell movement, cell development and cellular organization programs. Consistent with our findings that XRN2 impairs DNA damage and tumor invasion; XRN2 loss results in R-loop formation in promoters of genes important for tumor invasiveness and DNA repair such as FOXM1 and Cyclin B1. These data suggest that the regulation of R-loop formation is an important determinant in tumor progression. Citation Format: Julio C. Morales, Tuyen T. Dang. Examining the role of RNA:DNA hybrids (r loops) in glioblastoma multiforme cell motility and invasion [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A045.

MEDICAL AND RADIOBIOLOGICAL ASPECTS OF RADIATION COMDPLICATIONS IN PATIENTS WITH ONCOGINECOLOGICAL PROFILE

Summary. Aim: to analyze the literature regarding the causes of the occurrence and features of distant complications of radiation therapy of cancer patients; investigation of the frequency and spectrum of spontaneous aberrations of chromosomes in the lymphocytes of peripheral blood of patients with oncogynecological profile (body cancer and cervix) before the onset of radiation therapy. Object and methods: peripheral blood lymphocyte test system with metaphase analysis of chromosome aberrations of 32 primary of cancer patients (follow-up group) and 30 conditionally healthy donors (comparison group). The examination of patients was performed before the onset of radiation therapy. Results: based on the analysis of literature data, the path to a personalized approach to the planning of radiation therapy for patients with oncogyne5 cological profile, the treatment of which is complicated by radiation lesions from the organs and tissues of the pelvis. The clinical and radiobiological aspects of the formation of radiation complications are considered in detail, the search for genetic indicators for the detection of patients with a high risk of developing radiation complications is justified. The results of cytogenetic examinations of patients with endometrial cancer and cervical cancer are close and indicate a 6-fold increase in the frequency of spontaneous chromosome aberrations compared to the population rate. In the spectrum of chromosomal restructures, complex restructures are recorded, which is uncharacteristic of the spontaneous level of aberration in healthy donors, as well as increased levels of chromatide type aberrations. Conclusions: the increased level of spontaneous chromosomal aberrations in T-lymphocytes of primary oncogynecological patients and the predominance of chromatid-type aberrations in the spectrum of registered chromosomal rearrangements indicate that genetic instability is formed in healthy cells before the start of radiation therapy, which predicts the risk of distant radiation complications, including the occurrence of secondary tumors radiation genesis. The examination of patients with the use of cytogenetic test will provide the most reasonable conclusion about the individual radio sensitivity of the patient to the onset of radiation therapy and will contribute to increasing its effectiveness, as well as improving the quality of life.

Spontaneous Chromosomal Aberrations in Lymphocytes and Development of Tumor in Hospital Workers.

Cytogenetic analysis of chromosomes in blood lymphocytes can be used to reveal biomarkers of tumor risk. The frequency of chromosomal aberrations (CAs) appears to correlate with the later incidence of cancer. In our work, a total of 515 healthy Hungarian medical workers and 725 controls were enrolled in our investigation. The CAs in peripheral blood lymphocytes were analyzed. The frequency of CAs was significantly higher in the groups working with ionizing radiation and with cytostatic agents compared to unexposed controls and in male smokers rather than non-smokers. The frequency of dicentric chromosomes, however, was not significantly different between control and exposed groups. Among 82 cancer cases (6.6%), the most frequent types were cancer of the breast (20.5%), colon (12.8%), lung and thyroid gland (9-9%). Our analysis showed 8.1% cancer cases in smokers compared to 5.7% in non-smokers. The potential exposure to carcinogens did not modify the effect of CAs on cancer risk but tobacco smoking did increase risk.

Spontaneous and induced chromosomal aberrations in peripheral blood of women with endometriosis: evidence of genomic instability.

Endometriosis is a prevalent gynecological disease which can lead to certain types of cancers. We investigated the spontaneous and induced chromosomal aberrations in peripheral blood lymphocytes (PBL) of endometriosis patients. We performed a pilot study utilizing mitomycin C (MMC) to assess chromosomal instability in the peripheral blood of participants. The patient group consisted of 20 infertile endometriosis patients and the controls of 20 healthy fertile women. Blood samples were collected, and two distinct lymphocyte cultures were prepared to evaluate the baseline and the MMC induced chromosomal aberrations. The results showed a significant difference before and after MMC treatment in both groups (P<0.001) and also revealed that endometriosis patients are far more sensitive to MMC than controls (P<0.001). The significantly higher frequency of induced and spontaneous chromosomal aberrations in patients can be consider as a sign of genomic instability and the defect in DNA repair mechanisms, which can be both assumed as a driver of cancer development in endometriosis patients.

Effects of brachytherapy on cytogenetic parameters and oxidative status in peripheral blood lymphocytes of gynecologic cancer patients.

The state-of-the-art brachytherapy technologies with high-dose sources of 60Co and 192Ir within contemporary treatment protocols for cancer patients allow achieving maximum dose distribution in the clinical target and with minimum radiation exposure of surrounding organs and tissues. For minimization and overcoming the early and late radiation complications, development of respective radiobiological criteria along with perfecting of physical and technical characteristics of the ionizing radiation sources are required. To study the effect of 192Ir radiation on the chromosomal aberrations and prooxidant/antioxidant status of blood lymphocytes in gynecological cancer patients. The patients (n= 45) with endometrial, cervical and secondary cancer of vagina were enrolled in the study. For brachytherapy, the irradiation of vaginal mucosa was conducted using "GammaMed plus" device for contact radiation therapy with 192Ir source. Prior to irradiation and in 20-24h after brachytherapy session, the venous blood samples were obtained and peripheral blood lymphocytes (PBL) were cultured for cytogenetic analysis. The prooxidant/antioxidant status was determined in hemolysates by the method of hydrogen peroxide-induced chemiluminescence. The average level of spontaneous chromosome aberrations in PBL of the patients was (7.8± 0.4) per 100metaphases, which is more than twice higher than the upper limit of the average population values. The frequency of chromosome aberrations in PBL of patients after brachytherapy session was (15.3± 1.0) per 100metaphases. An increased intensity of O2- generation by PBL after brachytherapy session was also noticed. Local irradiation at a dose of 6Gy featuring the first dose fraction of brachytherapy induces extra chromosomal aberrations in PBL of gynecological cancer patients and intensifies prooxidant processes in the blood.

Spontaneous and Radiation-Induced Chromosome Aberrations in Primary Fibroblasts of Patients With Pediatric First and Second Neoplasms.

The purpose of the present study was to investigate whether former childhood cancer patients who developed a subsequent secondary primary neoplasm (SPN) are characterized by elevated spontaneous chromosomal instability or cellular and chromosomal radiation sensitivity as surrogate markers of compromised DNA repair compared to childhood cancer patients with a first primary neoplasm (FPN) only or tumor-free controls. Primary skin fibroblasts were obtained in a nested case-control study including 23 patients with a pediatric FPN, 22 matched patients with a pediatric FPN and an SPN, and 22 matched tumor-free donors. Clonogenic cell survival and cytogenetic aberrations in Giemsa-stained first metaphases were assessed after X-irradiation in G1 or on prematurely condensed chromosomes of cells irradiated and analyzed in G2. Fluorescence in situ hybridization was applied to investigate spontaneous transmissible aberrations in selected donors. No significant difference in clonogenic survival or the average yield of spontaneous or radiation-induced aberrations was found between the study populations. However, two donors with an SPN showed striking spontaneous chromosomal instability occurring as high rates of numerical and structural aberrations or non-clonal and clonal translocations. No correlation was found between radiation sensitivity and a susceptibility to a pediatric FPN or a treatment-associated SPN. Together, the results of this unique case-control study show genomic stability and normal radiation sensitivity in normal somatic cells of donors with an early and high intrinsic or therapy-associated tumor risk. These findings provide valuable information for future studies on the etiology of sporadic childhood cancer and therapy-related SPN as well as for the establishment of predictive biomarkers based on altered DNA repair processes.

An Evaluation of Anti-Clastogenic Activities for Garlic (Allium Sativum), Turmeric (Curcuma Longa) and Tulsi (Ocimum Tenuiflorum) with Clastogen (Mitomycin) in Human Lymphocytes – A Case Study

Chromosomal aberrations based human syndrome are very critical and sometimes leads to lethality. Such syndrome or disorders are often irreversible. In this present study, we evaluated the preventing effect of herbal extracts from Ocimum (tulsi), Curcuma (turmeric) and Allium (garlic) in developing chromosomal aberrations in whole blood human lymphocytes. The results showed that the clastogenic effect was minimised by the combination of all three herbal extracts compared to the individual extract effects. The spontaneous chromosomal aberrations caused in lymphoma cells were also minimized by the herbal extracts.

Bi-allelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes

SPONASTRIME dysplasia is an autosomal-recessive spondyloepimetaphyseal dysplasia characterized by spine (spondylar) abnormalities, midface hypoplasia with a depressed nasal bridge, metaphyseal striations, and disproportionate short stature. Scoliosis, coxa vara, childhood cataracts, short dental roots, and hypogammaglobulinemia have also been reported in this disorder. Although an autosomal-recessiveinheritance pattern has been hypothesized, pathogenic variants in a specific gene have not been discovered in individuals with SPONASTRIME dysplasia. Here, we identified bi-allelic variants in TONSL, which encodes the Tonsoku-like DNA repair protein, in nine subjects (from eight families) with SPONASTRIME dysplasia, and four subjects (from three families) with short stature of varied severity and spondylometaphyseal dysplasia with or without immunologic and hematologic abnormalities, but no definitive metaphyseal striations at diagnosis. The finding of early embryonic lethality in a Tonsl-/- murine model and the discovery of reduced length, spinal abnormalities, reduced numbers of neutrophils, and early lethality in a tonsl-/- zebrafish model both support the hypomorphic nature of the identified TONSL variants. Moreover, functional studies revealed increased amounts of spontaneous replication fork stalling and chromosomal aberrations, as well as fewer camptothecin (CPT)-induced RAD51 foci in subject-derived cell lines. Importantly, these cellular defects were rescued upon re-expression of wild-type (WT) TONSL; this rescue is consistent with the hypothesis that hypomorphic TONSL variants are pathogenic. Overall, our studies in humans, mice, zebrafish, and subject-derived cell lines confirm that pathogenic variants in TONSL impair DNA replication and homologous recombination-dependent repair processes, and they lead to a spectrum of skeletal dysplasia phenotypes with numerous extra-skeletal manifestations.

Frequency of Spontaneous and Radiation-Induced Chromosomal Aberrations in Peripheral Blood Lymphocytes of Individuals of Different Ages

The frequency of spontaneous and X-ray-induced (0.25 Gy) in vitro chromosomal aberrations, as well as the level of chromosomal instability as a result of the bystander effect, in the blood lymphocytes of individuals aged from 12 to 102 years has been investigated using GTG staining of human metaphase chromosomes. The average group frequency of spontaneous chromosomal aberrations in adolescents (12–16 years), middle-aged people (33–52 years), and centenarians (90–102 years) was identical (p > 0.05), whereas it was higher in elderly people (60–70 years) due to increase of chromatid type aberrations rate (p 0.05); however, the total frequency of chromosomal aberrations in individuals aged 60–70 years exceeded the value of such indices in other age groups due to the chromosomal type damages (p < 0.05). In nonirradiated blood lymphocytes of adolescents, middle-aged, and elderly individuals cocultivated with lymphocytes irradiated in vitro (0.25 Gy), the induction of the bystander effect was detected. In lymphocytes of centenarians, the development of the bystander effect was not detected.

Genome damage in children with classical Ehlers-Danlos syndrome - An in vivo and in vitro study

Ehlers-Danlos syndrome (EDS) is a heritable connective tissue disorder characterized by skin hyperextensibility, abnormal wound healing, and joint hypermobility with prevalence 1:20 000. Its incidence is probably underestimated due to unknown number of subjects having mild symptoms who may have never been diagnosed through entire life time. Classical EDS is characterized by pathogenic variants of genes encoding type V collagen. The biological effects and health risks of patients with EDS exposure to low doses of ionizing radiation is poorly understood. The aim of this study was to investigate biological effect of low doses of ionizing radiation in children with EDS. Background values of chromosome aberrations in children suffering from classical EDS were determined and compared with control subjects. The in vitro experiment was performed by γ-irradiation of blood lymphocytes from EDS patients and healthy subjects at low doses (0.1, 0.2 and 0.3 Gy). Results show a significant increase level of spontaneous and radiation-induced chromosomal aberrations in children suffering from EDS in comparison with the control subjects (p < 0.05). In conclusion, children with EDS express higher background chromosome aberration frequency and increased radiosensitivity. These findings suggest specific susceptibility of EDS patients and importance of future investigation on risks of diagnostics and therapy which include radiation and genotoxic agents.

Rad54/Rad54B deficiency is associated to increased chromosome breakage in mouse spermatocytes.

Rad54 protein is a key player of the homologous recombination pathway, required for deposition and stabilisation of Rad51 foci at double strand breaks. Its role at the meiotic prophase, when double strand breaks are physiologically introduced to allow recombination, is well described. However, the hypothesis that Rad54 deficiency affect chromosome integrity of germ cells in unirradiated and irradiated animals has not been tested yet. In this study, the occurrence of spontaneous and X-ray-induced chromosome aberrations was assessed by analysis of spermatocyte MI spreads or by application of micronucleus assay in early spermatids isolated from wild type and Rad54/Rad54B knockout (KO) mice. In Rad54/Rad54B KO mice, the spontaneous chromosome aberration frequency detected at MI was >10-fold higher than in wild type animals. In addition, after exposure to 1 Gy X-rays at the radiosensitive stage of diplotene, an enhanced response to radiation was observed in Rad54-deficient animals, corresponding to a 2-3 sensitivity factor in comparison to wild type mice. Also the spontaneous frequency of micronucleated round spermatids was on the average 10-fold higher in KO than in wild type mice, indicating that Rad54/Rad54B KO spermatocytes carrying chromosome aberrations are able to pass through the meiotic divisions and to continue the spermatogenesis process. Our results provide the first evidence of the role of Rad54/Rad54B in the maintenance of a stable karyotype during male meiosis, and suggest that Rad54/Rad54B deficiency may impact on the DNA integrity of developing mouse gametes.

Clonal chromosomal and genomic instability during human multipotent mesenchymal stromal cells long-term culture

Background aimsSpontaneous mutagenesis often leads to appearance of genetic changes in cells. Although human multipotent mesenchymal stromal cells (hMSC) are considered as genetically stable, there is a risk of genomic and structural chromosome instability and, therefore, side effects of cell therapy associated with long-term effects. In this study, the karyotype, genetic variability and clone formation analyses have been carried out in the long-term culture MSC from human gingival mucosa.MethodsThe immunophenotype of MSC has been examined using flow cytofluorometry and short tandem repeat (STR) analysis has been carried out for authentication. The karyotype has been examined using GTG staining and mFISH, while the assessment of the aneuploidy 8 frequency has been performed using centromere specific chromosome FISH probes in interphase cells.ResultsThe immunophenotype and STR loci combination did not change during the process of cultivation. From passage 23 the proliferative activity of cultured MSCs was significantly reduced. From passage 12 of cultivation, clones of cells with stable chromosome aberrations have been identified and the biggest of these (12%) are tetrasomy of chromosome 8. The random genetic and structural chromosomal aberrations and the spontaneous level of chromosomal aberrations in the hMSC long-term cultures were also described.ConclusionsThe spectrum of spontaneous chromosomal aberrations in MSC long-term cultivation has been described. Clonal chromosomal aberrations have been identified. A clone of cells with tetrasomy 8 has been detected in passage 12 and has reached the maximum size by passage 18 before and decreased along with the reduction of proliferative activity of cell line by passage 26. At later passages, the MSC line exhibited a set of cells with structural variants of the karyotype with a preponderance of normal diploid cells. The results of our study strongly suggest a need for rigorous genetic analyses of the clone formation in cultured MSCs before use in medicine.

POLYMORPHISM OF DNA REPAIR GENE XPD Lys751Gln AND CHROMOSOME ABERRATIONS IN LYMPHOCYTES OF THYROID CANCER PATIENTS EXPOSED TO IONIZING RADIATION DUE TO THE CHORNOBYL ACCIDENT

XPD Lys751Gln polymorphisms were detected by polymerase chain reaction in 102 TC patients including 38 patients exposed to ionizing radiation due to Chornobyl disaster (Chornobyl recovery workers, evacuees, and the residents of contaminated areas), 64 patients without history of ionizing radiation exposure and 45 healthy residents of Ukraine as control group. In homozygous carriers of the minor allele XPD Gln751Gln, exposed to ionizing radiation, the significantly increased risk of TC (odds ratio = 3.66; p = 0.03; 95% confidence interval 1.04-12.84) was found. Among evacuees and residents of contaminated areas, homozygous carriers of the minor allele variants of XPD gene were characterized by the high level of spontaneous chromosome aberrations. TC patients without history of ionizing radiation exposure, being homozygous carriers of the allele XPD Lys751Lys, had significantly reduced frequency of chromosome-type aberrations. The carriage of homozygous minor allele of DNA repair gene XPD Gln751Gln is a risk factor for TC in persons from Ukrainian population exposed to ionizing radiation and is associated with the increased levels of chromosomal instability. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

Application of chromosomal microarray analysis for a cohort of Chinese patients with spontaneous miscarriage

To explore the relationship between spontaneous miscarriage and chromosomal aberrations identifiable with chromosomal microarray analysis (CMA). A total of 440 product-of-conceptions were collected for the CMA testing. Four hundred and seventeen of 440 specimens (94.7%) were successfully detected, among which 209 (50.1%) were chromosomal abnormalities. One hundred and twenty-nine (61.7%) of the 209 specimens were numerical chromosomal abnormalities, 40 specimens (19.1%) were structural anomalies, 38 specimens (18.1%) were mosaicisms, and 2 specimens (1.0%) showed regions of homozygosity. CMA analysis of products of-conception specimens can yield a higher diagnostic rate than conventional karyotyping. The identification of the cause of spontaneous miscarriage can facilitate estimation of recurrence risks for future pregnancies.

Introductory studies of bacterial effects on the course of mitosis in adventitious roots of Allium cepa L.

The level of spontaneous chromosome aberrations and other phenomena concomitant with mitoses in the meristematic cells of &lt;i&gt;Allium cepa&lt;/i&gt; L. adventitious roots grown in water, depends to a large extent on the intensity of bacteria multiplication. From the water culture two strains of bacteria, which were most numerous, were isolated - &lt;i&gt;Agrobacterium&lt;/i&gt; and &lt;i&gt;Flavobacterium&lt;/i&gt;. A supernatant from bacteria grown on Davis medium induced chromosome sticking together, c-mitoses and the formation of polyploid nuclei in the roots of onion.

Стан кісткової тканини, метаболічні та імунологічні порушення в патогенезі остеоартрозу в підлітковому віці

З метою попередження прогресування патологічних змін у суглобах у підлітків із остеоартрозом було вивчено стан кісткової тканини при початкових проявах захворювання і проаналізовано її взаємозв’язки з біохімічними, імунологічними та генетичними показниками. Структурно-функціональний стан кісткової тканини було досліджено за допомогою ультразвукової денситометрії у 51 підлітка (31 дівчина і 20 юнаків) віком 12–14 років (33,3 %) і 15–18 років (67,7 %) із встановленим діагнозом ініціальної стадії остеоартрозу колінних суглобів. Вивчено імунологічні (клітинний та гуморальний імунітет, уміст цитокінів), біохімічні (глікозаміноглікани і хондроїтинсульфати крові, уронові кислоти сечі, екскреція оксипроліну, активність кислої та лужної фосфатаз, колагенази, еластази, інгібіторів еластази, вміст кальцію, фосфору, магнію) та генетичні (частота спонтанних хромосомних аберацій) параметри.Виявлено значну частоту остеопенії (60,7 %), переважно першого ступеня, в осіб жіночої статі віком до 14 років при формуванні остеоартрозу на тлі реактивного артриту, зниженні висоти суглобового хряща і наявності синовіту. Аналіз взаємозв’язків показника Z-scorе з біохімічними та імунологічними параметрами, а також із рівнем хромосомних аберацій показав вірогідний вплив змін у різноманітних системах гомеостазу на стан кісткової тканини у підлітків із остеоартрозом.