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Chromosome aberrations (CAs), a genotoxic potential of carcinogens, are believed to contribute to tumorigenesis by chromosomal rearrangements through micronucleus formation. However, there is no direct evidence that proves the involvement of CAs in tumorigenesis in vivo. In the current study, we sought to clarify the involvement of CAs in chemical carcinogenesis using a rat model with a pure CA‐inducer hepatocarcinogen, acetamide. Whole‐genome analysis indicated that hepatic tumors induced by acetamide treatment for 26–30 weeks showed a broad range of copy number alterations in various chromosomes. In contrast, hepatic tumors induced by a typical mutagen (diethylnitrosamine) followed by a nonmutagen (phenobarbital) did not show such mutational patterns. Additionally, structural alterations such as translocations were observed more frequently in the acetamide‐induced tumors. Moreover, most of the acetamide‐induced tumors expressed c‐Myc and/or MDM2 protein due to the copy number gain of each oncogene. These results suggest the occurrence of chromosomal rearrangements and subsequent oncogene amplification in the acetamide‐induced tumors. Taken together, the results indicate that CAs are directly involved in tumorigenesis through chromosomal rearrangements in an acetamide‐induced hepatocarcinogenesis rat model. [ABSTRACT FROM AUTHOR]

BackgroundExcessive radon exposure is considered the second risk factor for lung cancer. Since the opening of the subway in a city of Zhejiang Province, the exposure level of radioactive gas radon in subway stations and its impact on occupational health have become one of the important issues of public concern. ObjectiveTo monitor the radon concentration of subways in a city in Zhejiang Province and explore the effect of radon exposure on chromosome aberration and micronuclei in the working population. MethodsA total of 55 vehicle control rooms of 55 stations affiliated to two different subway lines in a city were measured for one year; the 110 ticket offices and 55 security checkpoints from the same 55 stations were measured from 16 March to 14 June. The radon concentrations were compared by job types, subway lines, and seasons referring to Measurement methods for determination of radon in environmental air (HJ 1212-2021). Peripheral blood lymphocyte chromosome aberration and micronucleus analyses were conducted in 165 subway workers from monitoring sites for three different job types, then the influencing factors were analyzed. The detection methods were adopted from the standards of Test and assessment of chromosomal aberrations on occupational health examinations for radiation workers (GBZ/T 248-2014) and Standard for the method of micronucleus detection in lymphocytes on occupational health examination for radiation workers and exposure dose estimation (GBZ/T 328-2023). ResultsThe radon concentration range of the target subways in Zhejiang Province was 10-320 Bq·m−3, all lower than the national limit (≤400 Bq·m−3). The differences in radon radioactivity levels among different lines, job types, and time segments were statistically significant (P0.05). Chromosome aberration and micronuclei varied by age, subway station seniority, and smoking (P0.05). ConclusionThe radon concentration in the target subway system is at a normal level. The rates of chromosomal aberration and micronucleus formation vary by jobs, but both are lower than the corresponding national limits. Therefore, radon exposure has not yet caused outstanding health impact on the subway workers.

Withania somnifera (Ashwagandha) also called as Indian ginseng, a revered herb from Indian traditional system of medicine is a rejuvenator and tonic (Rasayana) used for its varied benefits. The roots of ashwagandha exhibit properties like anti-inflammatory, aphrodisiac, anthelmintic, astringent, diuretic, stimulant and thermogenic. However, data of ashwagandha on its mutagenic effects are lacking. In the present study, in-vitro genotoxicity tests were used to evaluate the mutagenic potential of Ashwagandha Root Extract (ARE). Concentrations of 0.156 to 5.00 mg/plate ARE were used for conducting Bacterial reverse mutation test (BRMT). For chromosome aberration (CA) test ARE was used in concentrations of 0.25 to 2.00 mg/ml, and for micronucleus (MN) tests ARE concentrations of 500/1000/2000 mg/kg were used. Acute oral toxicity was conducted in Wistar rats (n = 25) as per the OECD guideline (#423) with doses of 500/1000/2000 mg/kg body weight in male Swiss albino mice for morbidity and mortality for 3 days. The BRMT and CA tests were conducted with and without metabolic activation (S9). The study was approved by the institutional ethics committee (IEC) and institutional animal ethics committee (IAEC). ARE failed to show any mutagenic effects up to a dose of 5 mg/plate in BRMT. Also, ARE did not show any clastogenic activity in doses up to 2 mg/ml in CA test and in micronucleus test up to 2000 mg/kg body weight. These results were observed with and without metabolic activation (S9) under the stated experimental conditions. No mortality, morbidity, or any clinical signs were observed up to 3 days following ARE administration. Ashwagandha root extract failed to show any mortality in doses up to 2000 mg/kg oral dosage and did not show any mutagenic (genotoxic) effects in high concentrations.

Preimplantation genetic testing (PGT) is the earliest form of prenatal diagnosis that has become an established procedure for couples at risk of passing a severe genetic disease to their offspring. At UMC Ljubljana, we conducted a retrospective register-based study to present 15 years of PGT service within the public healthcare system in Slovenia. We collected the data of the PGT cycles from 2004 to 2019 and compared clinical outcomes for chromosomal and monogenic diseases using different embryo biopsy and testing approaches. In addition, we assessed the extent to which PGT has become the preferred option compared to classic prenatal diagnostics. We treated 211 couples, 110 with single gene disorder, 88 with structural chromosome rearrangement and 13 for numerical chromosome aberration. There were 375 PGT cycles with oocyte retrieval, while embryo transfer was possible in 263 cases resulting in 78 deliveries and 84 children. Altogether, the clinical pregnancy rate per embryo transfer was 31% in 2004–2016 (blastomere biopsy) and 43% in 2017–19 (blastocyst biopsy), respectively. We assessed that approximately a third of couples would opt for PGT, while the rest preferred natural conception with prenatal diagnosis. Our results show that providing a PGT service within the public healthcare system has become a considerable option in pregnancy planning for couples at risk of transmitting a severe genetic disease to their offspring. In Slovenia, approximately a third of couples would opt for PGT. Although the number of cycles is small, our clinical results are comparable to larger centres.

Lung cancer has the highestmortality rate among all cancers worldwide. The 5-year overall survival rate for non-small cell lung cancer (NSCLC) is estimated at around 26%, whereas for small cell lung cancer (SCLC), the survival rate is only approximately 7%. This disease places a significant financial and psychological burden on individuals worldwide. The symbiotic microbiota in the human body has been significantly associated with the occurrence, progression, and prognosis of various diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Studies have demonstrated that respiratory symbiotic microorganisms and their metabolites play a crucial role in modulating immune function and contributing to the pathophysiology of lung cancer through their interactions with the host. In this review, we provide a comprehensive overview of the microbial characteristics associated with lung cancer, with a focus on the respiratory tract microbiota from different locations, including saliva, sputum, bronchoalveolar lavage fluid (BALF), bronchial brush samples, and tissue. We describe the respiratory tract microbiota's biodiversity characteristics by anatomical region, elucidating distinct pathological features, staging, metastasis, host chromosomal mutations, immune therapies, and the differentiated symbiotic microbiota under the influence of environmental factors. Our exploration investigates the intrinsic mechanisms linking the microbiota and its host. Furthermore, we have also provided a comprehensive review of the immune mechanisms by whichmicrobiota are implicated in the development of lung cancer. Dysbiosis of the respiratory microbiota can promote or inhibit tumor progression through various mechanisms, including DNA damage and genomic instability, activation and regulation of the innate and adaptive immune systems, and stimulation of epithelial cells leading to the upregulation of carcinogenesisrelated pathways. [ABSTRACT FROM AUTHOR]

Boron-Neutron Capture Therapy (BNCT) is a tumor-selective radiotherapy, based on the nuclear capture reaction 10B(n,α)7Li producing short range α-particles and recoiling 7Li nuclei exclusively confined to boron-enriched cancer cells. These particles possess high Linear Energy Transfer (LET) and mainly generate clustered DNA strand breaks, which are less faithfully restored by intracellular repair. Mis-rejoined breaks yield chromosome aberrations (CAs), which, for high-LET radiation, are more complex in nature than after sparsely ionizing photons/electrons used in conventional radiotherapy, which leads to increased cell-killing ability. However, such a radiobiological tenet of BNCT has been scantily studied at the DNA level. Therefore, the aim of this work was to evaluate CAs induced by BNCT in comparison to X-rays in genomically stable normal human epithelial mammary MCF10A cells. Two Fluorescence In Situ Hybridization (FISH)-based techniques were applied to calyculin A-induced prematurely condensed chromosomes: Whole Chromosome Painting and multicolor(m)-FISH. Not only did BNCT induce a greater CA frequency than X-ray irradiation, but m-FISH karyotype-wide analysis confirmed that CAs following BNCT exhibited a much higher degree of complexity compared to X-rays. To our knowledge, this is the first time that such evidence supporting the radiobiological superiority of BNCT has been shown. [ABSTRACT FROM AUTHOR]

Background. The search for optimal methods of selective and integral determination of various cytotoxic compounds in biological fluids and tissues, which would have high sensitivity and allow for quick and reliable assessment and detection of potentially cytotoxic components of substances with biologically active action, remains relevant today. It is known that chemotherapeutic agents can be released into the environment (air, surface water, sediments and soil) and cause adverse consequences (impact on the stability of ecosystems due to reduced viability of species). The aim of this work was to investigate the effect of thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl1-benzofuran-2-carboxamide (BF1) conjugated with PEG-based polymeric nanoparticles (PEG-PN – Th1) on genotoxicity and acute toxicity in allium bioassay. Materials and Methods. Allium cepa ana-telophase assay was applied to monitor genotoxicity of the studied compounds. The acute toxic effects such as inhibition of cell division, seed germination and growth of Allium roots were estimated. A. cepa seeds (15 per each point) were germinated on the studied solutions of BF1, Th1 and Th2 (10 μM) for 5 days at 22 °C. The root growth and the percentage of inhibition of seed germination were calculated. In order to establish cyto- and genotoxicity of the studied compounds, we have determined the mitotic index and the relative amount of chromosomal aberrations. Results. BF1 had a significant inhibitory effect on root growth and seed germination at a concentration of 10 μM. The effect was eliminated when it was influenced by BF1 complex with a polymeric carrier. The free polymer does not have a negative effect on the studied parameters either. A significant decrease in the mitotic index and increase in the percentage of chromosomal aberrations was observed under the action of BF1 at a concentration of 10 µM. There was no significant change in the value of mitoitic index and percentage of chromosomal aberrations under the action of Th2 comp­lex or polymeric carrier Th1. Conclusions. The thiazole derivative in complex with a polymeric carrier at a concentration of 10 µM did not show acute toxicity in Allium cepa bioassay. Polymer carrier based on polyethylene glycol neutralized the negative effect of BF1 on the mitotic and phase indices of Allium root meristem cells; it also decreased the percentage of chromosomal aberrations.

Abstract Background Ventricular septal defect (VSD) is the most common subtype of congenital heart disease. In the present study, we aimed to determine whether chromosome aberration was associated with the occurrence of VSD and evaluate the association of VSD size, location and chromosome aberration with adverse outcomes in the Chinese fetuses. Methods Fetuses with VSD and comprehensive follow-up data were included and evaluated retrospectively. Medical records were used to collect epidemiological data and foetal outcomes. For VSD fetuses, conventional karyotype and microarray analysis were conducted. After adjusting confounding factors by using multivariable logistic regression analyses, the association between chromosome variations and VSD occurrence was explored. The association between defect size, location and chromosome aberrations and adverse foetal outcomes was also investigated. Results Chromosome aberration was the risk factor for VSD occurrence, raising 6.5-fold chance of developing VSD. Chromosome aberration, peri-membranous site and large defect size of VSD were significant risk factors of adverse fetal outcome. Chromosome aberrations, including pathogenic copy number variations (CNVs) and variations of uncertain significance (VUS), were both risk factors, increasing the risk of the adverse fetal outcome by 55.9 times and 6.7 times, respectively. The peri-membranous site would increase 5.3-fold risk and defects larger than 5 mm would increase the 7.1-fold risk for poor fetal outcome. Conclusions The current investigation revealed that chromosomal abnormalities, large defects, and the peri-membranous site were all risk factors for poor fetal outcomes. Our study also indicated that chromosome aberration was one of risk factors for the VSD occurrence.

Citrinin （CIT） is a mycotoxin produced by several species of the genera Aspergillus， Penicillium， and Monascus， and it often contaminates grains and grain products. CIT shows clear nephrotoxicity， while its carcinogenicity evidence is insufficient. Considering the ability of genotoxicity tests to screen chemicals for potential carcinogenicity， the genotoxicity of CIT was reviewed from the perspective of three genetic endpoints， including genetic mutation， chromosomal aberrations， and DNA damage. CIT is a genotoxic substance that induces chromosomal aberrations. The mechanism may be related to its influence on tubulin polymerization and spindle formation during cellular mitosis， thereby causing cell cycle blocking. This study provides basic data for follow-up risk assessments of CIT.

Preimplantation genetic testing (PGT) is the earliest form of prenatal diagnosis that has become an established procedure for couples at risk of passing a severe genetic disease to their offspring. At UMC Ljubljana, we conducted a retrospective register-based study to present 15 years of PGT service within the public healthcare system in Slovenia. We collected the data of the PGT cycles from 2004 to 2019 and compared clinical outcomes for chromosomal and monogenic diseases using different embryo biopsy and testing approaches. In addition, we assessed the extent to which PGT has become the preferred option compared to classic prenatal diagnostics. We treated 211 couples, 110 with single gene disorder, 88 with structural chromosome rearrangement and 13 for numerical chromosome aberration. There were 375 PGT cycles with oocyte retrieval, while embryo transfer was possible in 263 cases resulting in 78 deliveries and 84 children. Altogether, the clinical pregnancy rate per embryo transfer was 31% in 2004–2016 (blastomere biopsy) and 43% in 2017–19 (blastocyst biopsy), respectively. We assessed that approximately a third of couples would opt for PGT, while the rest preferred natural conception with prenatal diagnosis. Our results show that providing a PGT service within the public healthcare system has become a considerable option in pregnancy planning for couples at risk of transmitting a severe genetic disease to their offspring. In Slovenia, approximately a third of couples would opt for PGT. Although the number of cycles is small, our clinical results are comparable to larger centres. [ABSTRACT FROM AUTHOR]

Even today when nearly 80 years have passed after the atomic bomb (A-bomb) was dropped, there are still debates about the exact doses received by the A-bomb survivors. While initial airborne kerma radiation (or energy spectrum of emitted radiation) can be measured with sufficient accuracy to assess the radiation dose to A-bomb survivors, it is not easy to accurately assess the neutron dose including appropriate weighting of neutron absorbed dose. Particularly, possible post-explosion exposure due to the radioactive particles generated through neutron activation have been almost neglected so far, mainly because of a large uncertainty associated to the behavior of those particles. However, it has been supposed that contribution of such non-initial radiation exposure from the neutron-induced radioactive particles could be significant, according to the findings that the stable chromosomal aberration rates which indicate average whole-body radiation doses were found to be more than 30% higher for those exposed indoors than for those outdoors even at the same initial dose estimated for the Life Span Study. In this Mini Review article, the authors explain that such apparently controversial observations can be reasonably explained by assuming a higher production rate of neutron-induced radioactive particles in the indoor environment near the hypocenter.

Uniparental disomy (UPD) refers to as both homologous chromosomes inherited from only one parent without identical copies from the other parent. Studies on clinical phenotypes in UPDs are usually focused on the documented UPD 6, 7, 11, 14, 15, and 20, which directly lead to imprinting disorders. This study describes clinical phenotypes and genetic findings of three patients with UPD 2, 9, and 14, respectively. Chromosomal microarray (CMA), UPDtool, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and wholeexome sequencing (WES) analysis were performed to characterize the genetic etiology. The CMA revealed a homozygous region involving the whole chromosome 2 and 9, a partial region of homozygosity in chromosome 14. UPD-tool revealed a paternal origin of the UPD2. MS-MLPA showed hypomethylation of imprinting gene MEG3 from maternal origin in the UPD14 case. In addition, UPD14 case displayed complex symptoms including growth failure, hypotonia and acute respiratory distress syndrome (ARDS), accompanied by several gene mutations with heterozygous genotype by WES analysis. Furthermore, we reviewed the documented UPDs and summarized the clinical characteristics and prognosis. This study highlighted the importance to confirm the diagnosis and origin of UPD using genetic testing. Therefore, it is suggested that expanding of the detailed phenotypes and genotypes provide effective guidance for molecule testing and genetic counseling, and promote further biological investigation to the underlying mechanisms of imprinted disorders and accompanied copy number variations. [ABSTRACT FROM AUTHOR]

Background: Ventricular septal defect (VSD) is the most common subtype of congenital heart disease. In the present study, we aimed to determine whether chromosome aberration was associated with the occurrence of VSD and evaluate the association of VSD size, location and chromosome aberration with adverse outcomes in the Chinese fetuses. Methods: Fetuses with VSD and comprehensive follow-up data were included and evaluated retrospectively. Medical records were used to collect epidemiological data and foetal outcomes. For VSD fetuses, conventional karyotype and microarray analysis were conducted. After adjusting confounding factors by using multivariable logistic regression analyses, the association between chromosome variations and VSD occurrence was explored. The association between defect size, location and chromosome aberrations and adverse foetal outcomes was also investigated. Results: Chromosome aberration was the risk factor for VSD occurrence, raising 6.5-fold chance of developing VSD. Chromosome aberration, peri-membranous site and large defect size of VSD were significant risk factors of adverse fetal outcome. Chromosome aberrations, including pathogenic copy number variations (CNVs) and variations of uncertain significance (VUS), were both risk factors, increasing the risk of the adverse fetal outcome by 55.9 times and 6.7 times, respectively. The peri-membranous site would increase 5.3-fold risk and defects larger than 5 mm would increase the 7.1-fold risk for poor fetal outcome. Conclusions: The current investigation revealed that chromosomal abnormalities, large defects, and the peri-membranous site were all risk factors for poor fetal outcomes. Our study also indicated that chromosome aberration was one of risk factors for the VSD occurrence. [ABSTRACT FROM AUTHOR]

During space travel, humans are continuously exposed to two major environmental stresses, microgravity (μG) and space radiation. One of the fundamental questions is whether the two stressors are interactive. For over half a century, many studies were carried out in space, as well as using devices that simulated μG on the ground to investigate gravity effects on cells and organisms, and we have gained insights into how living organisms respond to μG. However, our knowledge on how to assess and manage human health risks in long-term mission to the Moon or Mars is drastically limited. For example, little information is available on how cells respond to simultaneous exposure to space radiation and μG. In this study, we analyzed the frequencies of chromosome aberrations (CA) in cultured human lymphoblastic TK6 cells exposed to X-ray or carbon ion under the simulated μG conditions. A higher frequency of both simple and complex types of CA were observed in cells exposed to radiation and μG simultaneously compared to CA frequency in cells exposed to radiation only. Our study shows that the dose response data on space radiation obtained at the 1G condition could lead to the underestimation of astronauts' potential risk for health deterioration, including cancer. This study also emphasizes the importance of obtaining data on the molecular and cellular responses to irradiation under μG conditions.

To investigate the effects of low -dose ionizing radiation on the health of radiological medical staff. Methods A total of 386 radiological medical staff who underwent occupational health examinations at the Liaoning Provincial Center for Disease Control and Prevention from 2020 to 2021 were studied, and 174 staff who recently participated in the preand post -transfer health examinations for radiological posts were selected as the reference group. The blood cell counts, peripheral blood lymphocyte chromosome aberrations, and micronucleus rates of the two groups were analyzed. Results The lymphocyte count of the radiation workers was lower than that of the reference group, and the chromosome aberration rate and abnormality rate, micronucleus rate, and abnormality rate were higher than those of the reference group (P < 0.01). The results of multiple linear regression analysis showed that compared with the radiological medical staff who operated in separate rooms or male radiological medical staff, the lymphocyte count of the interventional therapists who operated in the same room near the table and female radiological medical staff was reduced (茁= - 0.182, - 0.159, P < 0.05); with the increase in working time, the lymphocyte count of radiological medical staff also decreased (茁= - 0.008, P < 0.05). The results of Poisson regression analysis showed that compared with the radiological medical staff who operated in separate rooms, the chromosome aberration rate and micronucleus rate of the interventional therapists increased (RR = 4.078, 1.359, P < 0.05); with the increase of working years, the chromosome aberration rate and micronucleus rate of the radiological medical staff also increased (RR = 1.050, 1.024, P < 0.05). Conclusions Long -term low -dose ionizing radiation had varying degrees of impact on lymphocyte count, peripheral blood lymphocyte chromosome aberration, and the micronucleus of radiological medical staff. Further occupational health monitoring should be strengthened for radiological medical staff engaged in interventional therapy to reduce radiation damage. [ABSTRACT FROM AUTHOR]

Forchlorfenuron (FCF, also known as CPPU), which belongs to the group of phenylurea cytokinins, is one of the most widely used synthetic plant growth regulators (PGRs) worldwide. Although FCF plays a crucial role in cellular growth and differentiation by promoting cell division in plants, it disrupts higher-order septin assembly in other eukaryotic organisms, including humans. Despite its widespread use, no study has been found investigating the genotoxic effects of this synthetic PGR on humans. Hence, this investigation was designed to examine the potential cyto-genotoxicity of a commercial formulation of FCF on human peripheral blood lymphocytes (PBLs) using chromosome aberrations (CAs) and mitotic index (MI) endpoints. The whole blood cultures were treated with 0.25, 0.50, 1.00, and 2.00 µg/ml concentrations of a commercial form of FCF. According to the results, FCF significantly enhanced the percentage of cells containing structural CAs at the concentrations of 1.00 and 2.00 µg/ml for both treatment times (24 and 48 h), in comparison to the negative control (P

There has been some controversy over the use of radiobiological models when modeling the dose-response curves of ionizing radiation (IR)-induced chromosome aberration and tumor prevalence, as those curves usually show obvious non-targeted effects (NTEs) at low doses of high linear energy transfer (LET) radiation. The lack of understanding the contribution of NTEs to IR-induced carcinogenesis can lead to distinct deviations of relative biological effectiveness (RBE) estimations of carcinogenic potential, which are widely used in radiation risk assessment and radiation protection. In this work, based on the initial pattern of two classes of IR-induced DNA double-strand breaks (DSBs) clustering in chromatin domains and the subsequent incorrect repair processes, we proposed a novel radiobiological model to describe the dose-response curves of two carcinogenic-related endpoints within the same theoretical framework. The representative experimental data was used to verify the consistency and validity of the present model. The fitting results indicated that, compared with targeted effect (TE) and NTE models, the current model has better fitting ability when dealing with the experimental data of chromosome aberration and tumor prevalence induced by multiple types of IR with different LETs. Notably, the present model without introducing an NTE term was adequate to describe the dose-response curves of IR-induced chromosome aberration and tumor prevalence with NTEs in low-dose regions. Based on the fitting parameters, the LET-dependent RBE values were calculated for three given low doses. Our results showed that the RBE values predicted by the current model gradually decrease with the increase of doses for the endpoints of chromosome aberration and tumor prevalence. In addition, the calculated RBE was also compared with those evaluated from other models. These analyses show that the proposed model can be used as an alternative tool to well describe dose-response curves of multiple carcinogenic-related endpoints and effectively estimate RBE in low-dose regions.

Previous research reported that prolonged benzene exposure during in utero fetal development causes greater fetal abnormalities than in adult-stage exposure. This phenomenon increases the risk for disease development at the fetal stage, particularly carcinogenesis, which is mainly associated with hematological malignancies. Benzene has been reported to potentially act via multiple modes of action that target the hematopoietic stem cell (HSCs) niche, a complex microenvironment in which HSCs and multilineage hematopoietic stem and progenitor cells (HSPCs) reside. Oxidative stress, chromosomal aberration and epigenetic modification are among the known mechanisms mediating benzene-induced genetic and epigenetic modification in fetal stem cells leading to in utero carcinogenesis. Hence, it is crucial to monitor exposure to carcinogenic benzene via environmental, occupational or lifestyle factors among pregnant women. Benzene is a well-known cause of adult leukemia. However, proof of benzene involvement with childhood leukemia remains scarce despite previously reported research linking incidences of hematological disorders and maternal benzene exposure. Furthermore, accumulating evidence has shown that maternal benzene exposure is able to alter the developmental and functional properties of HSPCs, leading to hematological disorders in fetus and children. Since HSPCs are parental blood cells that regulate hematopoiesis during the fetal and adult stages, benzene exposure that targets HSPCs may induce damage to the population and trigger the development of hematological diseases. Therefore, the mechanism of in utero carcinogenicity by benzene in targeting fetal HSPCs is the primary focus of this review. [ABSTRACT FROM AUTHOR]

Boron-Neutron Capture Therapy (BNCT) is a tumor-selective radiotherapy, based on the nuclear capture reaction 10B(n,α)7Li producing short range α-particles and recoiling 7Li nuclei exclusively confined to boron-enriched cancer cells. These particles possess high Linear Energy Transfer (LET) and mainly generate clustered DNA strand breaks, which are less faithfully restored by intracellular repair. Mis-rejoined breaks yield chromosome aberrations (CAs), which, for high-LET radiation, are more complex in nature than after sparsely ionizing photons/electrons used in conventional radiotherapy, which leads to increased cell-killing ability. However, such a radiobiological tenet of BNCT has been scantily studied at the DNA level. Therefore, the aim of this work was to evaluate CAs induced by BNCT in comparison to X-rays in genomically stable normal human epithelial mammary MCF10A cells. Two Fluorescence In Situ Hybridization (FISH)-based techniques were applied to calyculin A-induced prematurely condensed chromosomes: Whole Chromosome Painting and multicolor(m)-FISH. Not only did BNCT induce a greater CA frequency than X-ray irradiation, but m-FISH karyotype-wide analysis confirmed that CAs following BNCT exhibited a much higher degree of complexity compared to X-rays. To our knowledge, this is the first time that such evidence supporting the radiobiological superiority of BNCT has been shown.

Although mammalian fetuses have been suggested to be sensitive to radiation, an increased frequency of translocations was not observed in blood lymphocytes from atomic bomb (A-bomb) survivors who were exposed to the bomb in utero and examined as adults. Since experiments using hematopoietic cells of mice and rats confirmed this finding, it was hypothesized that either irradiated fetal hematopoietic stem cells (f-HSCs) cannot generate exchange-type chromosomal aberrations or cells bearing induced aberrations are eliminated before the animals reach adulthood. In the present study, pregnant mice (12.5–15.5 days post coitum [dpc]) were irradiated with 2 Gy of X-rays and long-term HSCs (LT-HSCs) were isolated 24 h later. Multicolor fluorescence in situ hybridization (mFISH) analysis of LT-HSC clones proliferated in vitro showed that nine out of 43 (21%) clones from fetuses and 21 out of 41 (51%) clones from mothers bore translocations. These results indicate that cells with translocations can arise in mouse f-HSCs but exist at a lower frequency than in the mothers 24 h after X-ray exposure. Thus, it seems likely that translocation-bearing f-HSCs are generated but subsequently disappear, so that the frequency of lymphocyte translocations may decrease and reach the control level by the time the animals reach adulthood. [ABSTRACT FROM AUTHOR]

Millions of people around the world are exposed to low doses of ionizing radiation from diagnostic computed tomography (CT) scans. Currently available data on the potential cancer risk after CT scans are contradictory and therefore demand further investigations. The aim of the current study was to obtain estimations of genome damage after CT scans in 42 non-cancer patients and to conduct a comparison of the results with 22 control subjects. The frequency of dicentric ring chromosomes and chromosome breaks was significantly increased in irradiated patients compared to the controls. The distribution of dicentrics among the cells demonstrated non-Poisson distribution that reflected non-uniform and partial-body radiation exposure. A fraction of patients followed Poisson distribution, which is typical for uniform whole-body exposures. Some patients demonstrated a level of dicentrics similar to the control subjects. The individual variations in the frequency and dicentric distribution suggested complex mechanisms of chromosome aberration induction and elimination that could be associated with individual radiosensitivity, as well as previous diagnostics that used ionizing radiation or the redistribution of small fractions of irradiated lymphocytes within the circulatory pull. In conclusion, CT scans may cause genome damage and possible increases in cancer risk. The introduction of a specific follow-up of such patients, especially in the case of repeated CT scans, is suggested. [ABSTRACT FROM AUTHOR]

Chromosomal translocations in cancer as well as benign neoplasias typically lead to the formation of fusion genes. Such genes may encode chimeric proteins when two protein-coding regions fuse in-frame, or they may result in deregulation of genes via promoter swapping or translocation of the gene into the vicinity of a highly active regulatory element. A less studied consequence of chromosomal translocations is the fusion of two breakpoint genes resulting in an out-of-frame chimera. The breaks then occur in one or both protein-coding regions forming a stop codon in the chimeric transcript shortly after the fusion point. Though the latter genetic events and mechanisms at first awoke little research interest, careful investigations have established them as neither rare nor inconsequential. In the present work, we review and discuss the truncation of genes in neoplastic cells resulting from chromosomal rearrangements, especially from seemingly balanced translocations. [ABSTRACT FROM AUTHOR]

The genotoxic and cytotoxic effects of aqueous leaf extract of calamansi (Citrus microcarpa Bunge) on the onion (Allium cepa L.) root tip cells were investigated in this study. The onion root tip cells showed decreased mitotic indices when the concentration of the calamansi leaf extracts was increased. Chromosomal aberrations were observed, such as multiple nuclei, strap nucleus, and pyknotic cells in onion root cells treated with varying concentrations. No chromosomal aberration was observed in control (distilled water). These results indicate that intake of medicinal plants with unregulated dosage may cause genetic damage.

Male infertility is caused by spermatogenetic failure, clinically noted as oligoor azoospermia. Approximately 20% of infertile patients carry a genetic defect. The most frequent genetic defect leading to azoospermia (or severe oligozoospermia) is Klinefelter syndrome (47, XXY), which is numerical chromosomal abnormality and Y- structural chromosome aberration. The human X chromosome is the most stable of all human chromosomes. The X chromosome is loaded with regions of acquired, rapidly evolving genes. The X chromosome may actually play an essential role in male infertility and sperm production. Here we will describe X chromosome aberrations, which are associated with male infertility.

Topiramate (sulfamate - substituted monosaccharide) a weight loss drug used a pharmacotherapeutic agent for obesity, a study was performed to evaluate the effect of the topiramate to induce chromosome aberrations (CA) and sister chromatid exchange (SCE) in lymphocytes of obesity patients. CA and SCE, a sensitive measure of chromosome damage, were counted in peripheral blood lymphocytes from 32 obesity patients treated with topiramate dose (6 months with 81mg/day, 12 months with 129 mg/day) and 16 healthy person as control group who had never received topiramate and other drugs during the period of the study. All of the treated patients with topiramate, have cells with CA and abnormal SCE frequencies, in analysis, obesity patients, was significantly increased CA in 129mg/day and 81mg/day topiramate dose compared with control (4.08±1.51 and 3.56±1.21) respectively, vs (1.40± 0.81), (P<0.01). Furthermore, a significantly higher SCE/Cell frequency (10.42 ±0.75and 8.75±0.38) in treated obesity patients with 129 mg/day, 81mg/day dose respectively comparison with their control group (5.91±0.31), (P<0.001). The chromosome damage and genotoxics are related to the daily dose and may be determined by the duration of treatment. We conclude the patients treatment with topiramate may be associated with genetic toxicity according to byproducts of drug metabolism. [ABSTRACT FROM AUTHOR]

This study aimed to investigate chromosomal aberrations of Eurycoma longifolia Jack (EL) root extract in human lymphocytes in vitro. Human whole blood was cultured in medium solution that treated with distilled water, 20% DMSO, extract of EL roots at the concentration of 2.5, 5, 10, 20, 40, 80 µg/mL (extracted with distilled water and ethanol), and nontreated (blank: only culture medium and whole blood). All experiments were cultured for 72 hours in the 37°C incubator. The effects of EL roots extract on cytotoxicity were compared with the control groups including the blank, distilled water, and 20% DMSO. This study found that EL root extract significantly decreased metaphase cell number and increased chromosome aberrations dose dependent manner (p<0.01). The 7 types of chromosome aberration that were observed consisted of dicentric chromosome, single chromatid breaks, isochromatid break, isochromatid gap, single chromatid gap, fragmentation, and deletion. The dicentric chromosome was the most common chromosomal aberrations type that was treated with EL root extract both distilled water and ethanol. Moreover, the ethanolic extract of EL root was more effective to stimulate chromosome aberrations compared to the water extract of EL root (the deletion and fragmentation were not found in the water extract of EL root). This study demonstrated that the phytochemicals of EL root extract had cytotoxicity effect (decreased metaphase cells and increase cells death) and genotoxic effect (increased chromosomal aberrations. The use of EL root crude extract with distilled water is therefore safer for cells. However, when EL is used at high levels, it may lead to the inhibition of cell division process and cause side effects (toxicity). EL extracts consist of various phytochemicals with different properties and dosages, thus more studies should be conducted on the effect of those substances on cytotoxicity, especially their effects on genotoxicity humans. [ABSTRACT FROM AUTHOR]

Ionizing radiation causes chromosome aberrations, which are possible biomarkers to assess space radiation cancer risks. Using the Monte Carlo codes Relativistic Ion Tracks (RITRACKS) and Radiation-Induced Tracks, Chromosome Aberrations, Repair and Damage (RITCARD), we investigated how geometrical properties of the cell nucleus, irradiated with ion beams of linear energy transfer (LET) ranging from 0.22 keV/μm to 195 keV/μm, influence the yield of simple and complex exchanges. We focused on the effect of (1) nuclear volume by considering spherical nuclei of varying radii; (2) nuclear shape by considering ellipsoidal nuclei of varying thicknesses; (3) beam orientation; and (4) chromosome intermingling by constraining or not constraining chromosomes in non-overlapping domains. In general, small nuclear volumes yield a higher number of complex exchanges, as compared to larger nuclear volumes, and a higher number of simple exchanges for LET < 40 keV/μm. Nuclear flattening reduces complex exchanges for high-LET beams when irradiated along the flattened axis. The beam orientation also affects yields for ellipsoidal nuclei. Reducing chromosome intermingling decreases both simple and complex exchanges. Our results suggest that the beam orientation, the geometry of the cell nucleus, and the organization of the chromosomes within are important parameters for the formation of aberrations that must be considered to model and translate in vitro results to in vivo risks. [ABSTRACT FROM AUTHOR]

Abstract Background Scholars agree that Torbjörn Caspersson’s lab at the Institute of Medical Cell Research and Genetics at the Karolinska Institute, Sweden, played a key role in the first description of the so-called Q-banding technique. It laid the foundation for a new era of cytogenetic diagnostics and had a lasting impact in several areas of biology and medicine. Methods Based on a mixed-method approach, essential aspects of the history of human cytogenetics are considered via primary and secondary analysis of biographical interviews as well as the qualitative evaluation of bibliometrics. Drawing on interviews with colleagues of lab member Lore Zech (1923–2013) and contemporary publications, this paper illuminates the role of and contribution by Zech: To what extent is the discovery attached to her and what does her legacy look like today? Results The analysis of the contemporary witness interviews with colleagues, students and junior researchers shows that Lore Zech was a committed member of Caspersson's research group. In addition, memoirs by contemporary colleagues describe her outstanding skills in microscopy. The different sources paint a multifaceted picture. In addition to the historians' patterns of interpretation, different legacies can also be found within the peer group. Conclusions We argue that Zech represent the type of scientist who, although her research was acknowledged with several prizes, so far has not been part of the canon of pioneers of international cytogenetics.

Several environmental pollutants can cause damage to chromosomes, one of which is the heavy metal NiNO3. Some plant extracts have antigenotoxic properties that resulted in a decrease in chromosomal damage. Member of flowering plants that need to be tested is seagrass. One seagrass species is Enhalus acoroides was found to contain phytochemical compounds. This study aimed to analysed the genotoxic effect and the potential of encapsulated E. acoroides leaf extract as antigenotoxic against nickel nitrate NiNO3. The extraction was conducted using a mixture of chloroform and ethanol and encapsulation of crude extract was done using maltodextrin and tween 80. Chromosomal aberrations were evaluated using the squash technique of Allium cepa var. aggregatum root tips. Triphenyltetrazolium chloride and Evans Blue staining were used to observe mitochondrial and apoptotic activities. The results showed that at higher concentrations the encapsulated E. acoroides extract showed a decrease of mitotic indices, however, there was no chromosome aberration observed. NiNO3 itself induced a genotoxic effect as observed by low mitotic index and a high percentage of chromosome aberration. The modulation of NiNO3 effect by the addition of the encapsulated E. acoroides extract at low concentration increase mitotic indicex but did not reduce chromosome aberration. Simultaneous Ni and encapsulated E. acoroides extract significantly reduce nuclear abnormalities such as nuclear fragmentation, nuclear lesion, and the formation of micronucleus suggesting the potential of the extract as antigenotoxic.

Nowadays, ordinary people can travel in space, and the possibility of extended durations in an environment such as moon of the Earth and Mars with higher space radiation exposures compared to past missions, is increasing. Until now, the physical doses of space radiation have been measured, but measurement of direct biological effects has been hampered by its low dose and low dose-rate effect. To assess the biological effects of space radiation, we launched and kept frozen mouse embryonic stem (ES) cells in minus eighty degree Celsius freezer in ISS (MELFI) on the International Space Station (ISS) for a maximum of 1,584 days. The passive dosimeter for life science experiments in space (PADLES) was attached on the surface of the sample case of the ES cells. The physical dosimeter measured the absorbed dose in water. After return, the frozen cells were thawed and cultured and their chromosome aberrations were analyzed. Comparative experiments with proton and iron ion irradiation were performed at particle accelerators on Earth. The wild-type ES cells showed no differences in chromosomal aberrations between the ground control and ISS exposures. However, we detected an increase of chromosome aberrations in radio-sensitized histone H2AX heterozygous-deficient mouse ES cells and found that the rate of increase against the absorbed dose was 1.54-fold of proton irradiation at an accelerator. On the other hand, we estimated the quality factor of space radiation as 1.48 ± 0.2. using formulas of International Commission of Radiation Protection (ICRP) 60. The relative biological effectiveness (RBE) observed from our experiments (1.54-fold of proton) was almost equal (1.04-fold) to the physical estimation (1.48 ± 0.2). It should be important to clarify the relation between biological effect and physical estimates of space radiation. This comparative study paves a way to reveal the complex radiation environments to reduce the uncertainty for risk assessment of human stay in space.

Caryophyllideans are intestinal parasites of freshwater fishes, occupying a basal position among the 'true' tapeworms. We performed detailed cytogenetic analyses of the well-known caryophyllidean species Caryophyllaeus laticeps. For comparison, we also examined for the first time the chromosomes of Paracaryophyllaeus gotoi, a specific parasite of loaches in China. Both species showed a diploid chromosome number of 2n = 20, n = 10m. Chromomycin A3 (CMA3)/diamidino-2-phenylindole (DAPI) staining performed for the first time in the class Cestoda revealed CMA3+/DAPI− bands in the pericentromeric regions of the short arms of chromosome pair no. 7 in the karyotype of C. laticeps. Fluorescence in situ hybridization with the 18S rDNA probe confirmed the presence of a single cluster of major rDNA near the centromere on a pair of small chromosomes in both species. These findings support the hypothesis that the ancestral state in the family Caryophyllaeidae is a single interstitial cluster of major rDNA genes and thus one nucleolar organizer region per haploid genome. Our results, which we presented together with literature data plotted on a phylogenetic tree, show stability of caryophyllidean karyotypes at the genus level, but showed differences between genera without a clear phylogenetic signal. The data allowed us to at least formulate a hypothesis about the ancestral haploid chromosome number of n = 10 for the family Caryophyllaeidae and possibly for the sister family Capingentidae. In addition, we compared two populations of C. laticeps from water bodies with different levels of polychlorinated biphenyl contamination, showing a slightly increased incidence of chromosomal abnormalities at the contaminated site. [ABSTRACT FROM AUTHOR]

In completed research, ferrous gluconate -a food additive- used to preserve black color to prevent discoloration during storage in ripe black olives, and Allium cepa L. species. A. cepa L. roots were treated with different doses of ferrous gluconate. The effective concentration EC50 (0.068 g/l) was determined. A. cepa root tips were treated with EC50/2 (0.034 g/l), EC50 (0.068 g/l), 2XEC50 (0.136 g/l) dose for 24, 48, 72 hours, and afterward, the root tips were prepared for observation under the light microscope according to the method of preparing mitotic preparation. Chromosomal abnormality index (CAI) and genotoxic effect of ferrous gluconate in A. cepa root tip cells were determined. Repeated measurement ANOVA and TUKEY multiple comparison tests were used to investigate the effect of time and dose together on genotoxicity. C-mitosis, polyploidy, polar shifting in anaphase, polar shifting in telophase, equatorial plate shifting, laggard chromosome was observed by microscope. The highest CAI (70.16±4.85) was observed at 72h for 2XEC50 dose. Chromosomal aberration is also observed in control group. While the most common chromosomal aberration is determined as C-mitosis; The least observed chromosomal aberration is determined as polyploidy. Research results revealed that ferrous gluconate has a genotoxic effect on the root tip of A. cepa.

The continuous production and release into the environment of chemicals has revealed the need to determine their cytotoxicity and genotoxicity. Sulfonamide-aldehyde (SA) derivatives, whose biological activity properties vary in a wide spectrum, are frequently used in agriculture, medicine, pharmacy and many other fields. These compounds have an important cycle in the ecological system due to their use and diversity. In the present study, the potential cytotoxic and genotoxic effects of sulfonamide-aldehyde derivative were investigated using Allium test system with the concentrations of 6.25, 12.5, 25, 50, and 100 μM. In A. cepa cells, the increasing concentrations of SA caused cytotoxic effects by inducing nuclear lesions and inhibition of mitotic index. In addition, the increasing concentrations of SA caused genotoxic effects by inducing micronucleus and chromosome aberrations, which the most common ones are C-mitosis, sticky metaphase, and anaphase bridge. The results indicate that the concentration of 25 μM is EC50 in micronucleus, nuclear lesions, and chromosome aberrations; and 50 μM is EC50 in mitotic index (p lt; 0.05).

This study aimed to evaluate the aqueous extract of Quercus infectoria galls extract (QIGE) as anticlastogenic. The effect of QIGE was tested in mice (5 groups for each test) treated with 7, 12-dimethylbenz (a) anthracene (DMBA), the strong site-specific carcinogenic agent. In this study, the QIGE show no signs of toxicity, a single dose of DMBA (50 mg/kg) was injected intraperitoneally to Swiss albino mice caused a great increase in number of chromosomal aberrations, micronucleated polychromatic erythrocytes (MnPCEs) and reduction in the percentage of mitotic index (MI) (cytogenetic markers). Oral pre-treatment and post-treatment of QIGE for 14 days at dose 2 gm/kg b.w. daily to DMBA-treated animals greatly reduced in number of micronucleus formation, chromosomal abnormalities such as chromosomal break, chromatid breaks, ring chromosome, dicentric chromosome and fragments. Besides, mitotic index frequency increased comparing with the positive control. The data suggest that QIGE has potent anti-clastogenic effect against DMBA-induced genotoxicity in bone marrow cells of albino male mice and it may have a protective effect against the mutagenicity of the polynuclear aromatic hydrocarbons (PAH).

Introduction: Following the wide distribution of non-invasive prenatal genetic screening (NIPS), numerous studies have reported a decline in total invasive tests in the recent years, up to 50–70% in some countries. However, in Denmark and Israel we have not experienced these declines. The objective of our study was to evaluate the trends in NIPS and chromosomal microarray analysis (CMA) use in Denmark and Israel.Methods: This retrospective study was performed by data acquisition from the Danish Cytogenetics Central Registry throughout the years 2000–2019, and Israeli Public Health Services, Ministry of Health computerized database (from 2011).Results: Of the 1,243,956 live births registered in Denmark over the years 2000–2019, a relatively steady level of invasive testing around 6% was noted since 2004, as opposed to 13.0% in Israel based on 1,594,962 live births between 2011 and 2019. The average uptake of NIPS was 1.1 ± 0.5% in Denmark vs. 4.3% in Israel (2013–2019). Relatively steady rates of invasive testing were noted in both countries, compared to a slight decline in NIPS in the recent years.Discussion: The recent decrease in the rates of invasive testing in the NIPS era was not observed in Denmark or in Israel. These results imply that Danish and Israeli women and/or health providers might favor the high resolution and yield of CMA testing over the non-invasiveness of NIPS. We explore and discuss this phenomenon, based on five central factors.

Millions of people around the world are exposed to low doses of ionizing radiation from diagnostic computed tomography (CT) scans. Currently available data on the potential cancer risk after CT scans are contradictory and therefore demand further investigations. The aim of the current study was to obtain estimations of genome damage after CT scans in 42 non-cancer patients and to conduct a comparison of the results with 22 control subjects. The frequency of dicentric ring chromosomes and chromosome breaks was significantly increased in irradiated patients compared to the controls. The distribution of dicentrics among the cells demonstrated non-Poisson distribution that reflected non-uniform and partial-body radiation exposure. A fraction of patients followed Poisson distribution, which is typical for uniform whole-body exposures. Some patients demonstrated a level of dicentrics similar to the control subjects. The individual variations in the frequency and dicentric distribution suggested complex mechanisms of chromosome aberration induction and elimination that could be associated with individual radiosensitivity, as well as previous diagnostics that used ionizing radiation or the redistribution of small fractions of irradiated lymphocytes within the circulatory pull. In conclusion, CT scans may cause genome damage and possible increases in cancer risk. The introduction of a specific follow-up of such patients, especially in the case of repeated CT scans, is suggested.

The identification of mild fetal ventriculomegaly prompts further evaluation focused on determining whether additional structural anomalies, genetic abnormalities or congenital infections are present. The aim of this study is to evaluate the frequency of chromosomal aberrations in fetuses with isolated mild symmetrical ventriculomegaly and determine the risk for a fetus with isolated mild ventriculomegaly to have chromosomal abnormality in a back ground. Additionally, we have performed an evaluation of the chromosomal microarray findings in a series of five fetuses with isolated mild symmetrical ventriculomegaly and a normal karyotype. The retrospective observational study included karyotype evaluation of 102 fetuses with isolated mild symmetrical ventriculomegaly identified at the time of the routine midpregnancy scanning. In five cases array-CGH was performed and the obtained data were compared with the data in the bioinformatics databases. Among fetuses with isolated mild symmetrical ventriculomegaly chromosome aberrations were found in 2 (1,96%) fetuses. In both cases autosomal aneuploidy was detected, and those are trisomy 21 and trisomy 18, respectively. The finding of a mild symmetrical isolated ventriculomegaly on the routine ultrasound fetal exam in the second trimester had low sensitivity, but high specificity and negative predictive value in the prediction of chromosome anomalies. Copy number variants (microduplications/microdeletions) were detected in four cases (80%). A search for the similar variants in NCBI ClinVar, DECIPHER, OMIM and ENSEMBL data bases, revealed that the microdeletions/microduplications detected in four fetuses in our study cannot be related with ventriculomegaly development. Our findings suggest that karyotyping is not justified in fetuses with isolated mild symmetrical ventriculomegaly (10-15 mm), in a low risk population. Therefore, when mild fetal ventriculomegaly is found in a low risk population, additional non-invasive procedures for chromosome aberration screening (such as noninvasive prenatal screening based on cell-free fetal DNA) are recommended, before making the decision to perform invasive diagnostic procedures. [ABSTRACT FROM AUTHOR]

Background: Scholars agree that Torbjörn Caspersson's lab at the Institute of Medical Cell Research and Genetics at the Karolinska Institute, Sweden, played a key role in the first description of the so-called Q-banding technique. It laid the foundation for a new era of cytogenetic diagnostics and had a lasting impact in several areas of biology and medicine. Methods: Based on a mixed-method approach, essential aspects of the history of human cytogenetics are considered via primary and secondary analysis of biographical interviews as well as the qualitative evaluation of bibliometrics. Drawing on interviews with colleagues of lab member Lore Zech (1923–2013) and contemporary publications, this paper illuminates the role of and contribution by Zech: To what extent is the discovery attached to her and what does her legacy look like today? Results: The analysis of the contemporary witness interviews with colleagues, students and junior researchers shows that Lore Zech was a committed member of Caspersson's research group. In addition, memoirs by contemporary colleagues describe her outstanding skills in microscopy. The different sources paint a multifaceted picture. In addition to the historians' patterns of interpretation, different legacies can also be found within the peer group. Conclusions: We argue that Zech represent the type of scientist who, although her research was acknowledged with several prizes, so far has not been part of the canon of pioneers of international cytogenetics. [ABSTRACT FROM AUTHOR]

In cases of nuclear and radiological accidents, public health and emergency response need to assess the magnitude of radiation exposure regardless of whether they arise from disaster, negligence, or deliberate act. Here we report the establishment of a national reference dose–response calibration curve (DRCC) for dicentric chromosome (DC), prerequisite to assess radiation doses received in accidental exposures. Peripheral blood samples were collected from 10 volunteers (aged 20–40 years, median = 29 years) of both sexes (three females and seven males). Blood samples, cytogenetic preparation, and analysis followed the International Atomic Energy Agency EPR-Biodosimetry 2011 report. Irradiations were performed using 320 kVp X-rays. Metafer system was used for automated and assisted (elimination of false-positives and inclusion of true-positives) metaphases findings and DC scoring. DC yields were fit to a linear–quadratic model. Results of the assisted DRCC showed some variations among individuals that were not statistically significant (homogeneity test, P = 0.66). There was no effect of age or sex (P > 0.05). To obtain representative national DRCC, data of all volunteers were pooled together and analyzed. The fitted parameters of the radiation-induced DC curve were as follows: Y = 0.0020 (±0.0002) + 0.0369 (±0.0019) *D + 0.0689 (±0.0009) *D2. The high significance of the fitted coefficients (z-test, P < 0.0001), along with the close to 1.0 p-value of the Poisson-based goodness of fit (χ2 = 3.51, degrees of freedom = 7, P = 0.83), indicated excellent fitting with no trend toward lack of fit. The curve was in the middle range of DRCCs published in other populations. The automated DRCC over and under estimated DCs at low (2 Gy) doses, respectively, with a significant lack of goodness of fit (P < 0.0001). In conclusion, we have established the reference DRCC for DCs induced by 320 kVp X-rays. There was no effect of age or sex in this cohort of 10 young adults. Although the calibration curve obtained by the automated (unsupervised) scoring misrepresented dicentric yields at low and high doses, it can potentially be useful for triage mode to segregate between false-positive and near 2-Gy exposures from seriously irradiated individuals who require hospitalization.

Abstract The Panel received a mandate from the European Commission to assess the genotoxic potential of triazine amine based on available information submitted by the applicants. Available information includes experimental genotoxicity data on triazine amine, Quantitative Structure–Activity Relationship (QSAR) analysis and read across with structurally similar compounds. Based on the overall weight of evidence, the Panel, in agreement with the cross‐cutting Working Group Genotoxicity, concluded that there is no concern for the potential of triazine amine to induce gene mutations and clastogenicity; however, the potential to induce aneugenicity was not adequately investigated. For a conclusion, an in vitro micronucleus assay performed with triazine amine would be needed.

Ionizing radiation is a well-known carcinogen that causes genomic instability. However, the biological and carcinogenetic effects of occupational radiation exposure at low doses have not been extensively studied. The aim of this study was to assess chromosomal instability in power plant workers exposed to occupational radiation at low doses in South Korea. Chromosomal aberrations in the lymphocytes of 201 nuclear power plant workers and 59 sex-matched controls were measured. Chromosomal aberrations in the lymphocytes of 201 nuclear power plant workers (mean age: 41.4 ± 10.0 years) and 59 sex-matched controls (mean age: 47.2 ± 6.0 years) were measured. A total of 500 metaphases for each subject were scored randomly. The means of recent 1.5-year, recent 5.5-year, and cumulative exposed radiation doses among workers were 8.22 ± 7.0 mSv, 30.7 ± 22.0 mSv, and 158.8 ± 86.1 mSv, respectively. The frequency of chromosome-type and chromatid-type aberrations was significantly higher in workers than that in the control group (p < 0.001), and the frequency of chromosome-type aberrations among workers increased in a radiation dose-dependent manner (τ = 0.16, p = 0.005). Poisson regression analyses revealed that chromosome-type aberrations were significantly associated with recent 1.5-year dose after adjusting for confounding variables such as age, smoking, and alcohol intake, even when only the exposed worker was considered. Frequency of multi-aberrant cells (two or more chromosome aberrations within a cell) increased according to cumulative neutron exposure. Our study demonstrates that chromosome damage can be induced in nuclear power plant workers occupationally exposed to ionizing radiation at low doses below the occupational permissible dose limit. Furthermore, an increase in multi-aberrant cells may provide evidence for chronic neutron exposure in nuclear power plant workers. This study was performed to obtain baseline data for a surveillance program of workers occupationally exposed to ionizing radiation long-term.

This study aimed to evaluate the aqueous extract of Quercus infectoria galls extract (QIGE) as anticlastogenic. The effect of QIGE was tested in mice (5 groups for each test) treated with 7, 12-dimethylbenz (a) anthracene (DMBA), the strong sitespecific carcinogenic agent. In this study, the QIGE show no signs of toxicity, a single dose of DMBA (50 mg/kg) was injected intraperitoneally to Swiss albino mice caused a great increase in number of chromosomal aberrations, micronucleated polychromatic erythrocytes (MnPCEs) and reduction in the percentage of mitotic index (MI) (cytogenetic markers). Oral pretreatment and post-treatment of QIGE for 14 days at dose 2 gm/kg b.w. daily to DMBA-treated animals greatly reduced in number of micronucleus formation, chromosomal abnormalities such as chromosomal break, chromatid breaks, ring chromosome, dicentric chromosome and fragments. Besides, mitotic index frequency increased comparing with the positive control. The data suggest that QIGE has potent anti-clastogenic effect against DMBA-induced genotoxicity in bone marrow cells of albino male mice and it may have a protective effect against the mutagenicity of the polynuclear aromatic hydrocarbons (PAH). [ABSTRACT FROM AUTHOR]

The Panel received a mandate from the European Commission to assess the genotoxic potential of triazine amine based on available information submitted by the applicants. Available information includes experimental genotoxicity data on triazine amine, Quantitative Structure-Activity Relationship (QSAR) analysis and read across with structurally similar compounds. Based on the overall weight of evidence, the Panel, in agreement with the cross-cutting Working Group Genotoxicity, concluded that there is no concern for the potential of triazine amine to induce gene mutations and clastogenicity; however, the potential to induce aneugenicity was not adequately investigated. For a conclusion, an in vitro micronucleus assay performed with triazine amine would be needed. [ABSTRACT FROM AUTHOR]

In a sporadic case of autism and language deficit due to auditory processing defects, molecular genetic studies revealed that a chromosomal deletion occurred in the 13q12-->q13 region. No chromosome abnormalities were detected in the parents. We determined that the deletion occurred on the paternally derived chromosome 13. There are two previous reports of chromosome 13 abnormalities in patients with autism. The deletion in the subject described in this paper maps between the two chromosome 13 linkage peaks described by Bradford et al. (2001) in studies of subjects with autism and language deficits. The 9-Mb region deleted in the patient described here contains at least four genes that are expressed in brain and that play a role in brain development. They are NBEA, MAB21L1, DCAMKL1 and MADH9. These genes therefore represent candidate genes for autism and specific language deficits.

In a sporadic case of autism and language deficit due to auditory processing defects, molecular genetic studies revealed that a chromosomal deletion occurred in the 13q12-->q13 region. No chromosome abnormalities were detected in the parents. We determined that the deletion occurred on the paternally derived chromosome 13. There are two previous reports of chromosome 13 abnormalities in patients with autism. The deletion in the subject described in this paper maps between the two chromosome 13 linkage peaks described by Bradford et al. (2001) in studies of subjects with autism and language deficits. The 9-Mb region deleted in the patient described here contains at least four genes that are expressed in brain and that play a role in brain development. They are NBEA, MAB21L1, DCAMKL1 and MADH9. These genes therefore represent candidate genes for autism and specific language deficits.

Background: understanding the genomic alteration induced by ionizing radiation still remains to be a methodological challenge in genetic field. The energy released from this type of radiation can potentially causes structural and numerical alterations in lymphocytes, which in turn converts them into abnormal tumor cells. Chromosomal abnormalities associated with specific type of hematological malignancies are determinant factors in evaluation of radiation dose and its potential in harming the body. None the less early detection of chromosomal aberration (CA) is crucial in prognosis and selection of therapy for the people exposed to irradiations. The aim of this study was to explore a swift and accurate genetic test that identifies CAs in radiologist exposed to X-rays. In addition synergistic effect of other clastogens in irradiated workers was also evaluated. Material and methods: thirty four heparinized blood samples were obtained from radiology workers exposed to X-rays. Blood samples were cultured in RPMI 1640 and F-10 Medias with and without PHA stimulation. Lymphocytes were harvested, separated and arrested at metaphase and their chromosomes were analyzed by solid and G-Banding techniques. Lymphocytic CA was also analyzed through whole chromosome painting FISH. Results: of the 37 blood sample from workers, 60% had various structural aberrations in which both the frequency and type of CAs were intensified among tobacco smokers. Conclusion: the results did not show any significant differences between the genders but other carcinogen like smoking can significantly increases the rate of CAs