Chromosome Aberrations In Cells Research Articles

A whale of a tale: whale cells evade the driving mechanism for hexavalent chromium-induced chromosome instability.

Chromosome instability, a hallmark of lung cancer, is a driving mechanism for hexavalent chromium [Cr(VI)] carcinogenesis in humans. Cr(VI) induces structural and numerical chromosome instability in human lung cells by inducing DNA double-strand breaks and inhibiting homologous recombination repair and causing spindle assembly checkpoint (SAC) bypass and centrosome amplification. Great whales are long-lived species with long-term exposures to Cr(VI) and accumulate Cr in their tissue, but exhibit a low incidence of cancer. Data show Cr(VI) induces fewer chromosome aberrations in whale cells after acute Cr(VI) exposure suggesting whale cells can evade Cr(VI)-induced chromosome instability. However, it is unknown if whales can evade Cr(VI)-induced chromosome instability. Thus, we tested the hypothesis that whale cells resist Cr(VI)-induced loss of homologous recombination repair activity and increased SAC bypass and centrosome amplification. We found Cr(VI) induces similar amounts of DNA double-strand breaks after acute (24 h) and prolonged (120 h) exposures in whale lung cells, but does not inhibit homologous recombination repair, SAC bypass, or centrosome amplification, and does not induce chromosome instability. These data indicate whale lung cells resist Cr(VI)-induced chromosome instability, the major driver for Cr(VI) carcinogenesis at a cellular level, consistent with observations that whales are resistant to cancer.

A study of the genotoxicity, fertility and early embryonic development toxicity of rotigotine behenate extended-release microspheres.

Continuous dopaminergic stimulation (CDS) has become an important strategy for the development of drugs to treat Parkinson's disease (PD). Rotigotine behenate extended-release microspheres (RBEM) for injection represent a new treatment regime for CDS and are undergoing clinical trials. In this study, we aimed to investigate the effect of RBEM on genotoxicity, fertility and early embryonic development. We used the Ames test, Chinese hamster lung (CHL) cell chromosome aberration test and the mouse bone marrow micronucleus test, to evaluate the genotoxicity of RBEM. These tests were all negative, thus indicating that RBEM did not induce genotoxicity. In reproduction toxicity testing in male rats on obvious findings following intramuscular administration (i.m.) of RBEM at up to 540 mg/kg (P > 0.5), when female rats were administered with RBEM in the dose range of 60 to 540 mg/kg given (i.m.), there were clear effects on fertility and early embryonic development. These results indicated that RBEM could induce toxicity in female rats and exert effect on fertility and early embryonic development stage.

Efficacy and functionality of sugarcane original vinegar on mice.

Due to their bioactive compounds and beneficial health effects, functional foods and plant-based natural medicines are widely consumed. Due to its bioactivities, vinegar is one of them that helps humans. Sugarcane original vinegar (SOV) is a special vinegar made from sugarcane as a raw material through biological fermentation processes. The objective of this study was to assess the effects of sugarcane original vinegar on growth performance, immune response, acute oral toxicity, bacterial reverse mutation, mammalian erythrocyte micronucleus, mouse spermatogonial chromosome aberration, mammalian bone marrow cell chromosome aberration changes, and serum characteristics in mice. Distortion parameters were used to assess its safety, and at the same time, the functionality of SOV was monitored during experimentation. The results show that the SOV has no damage or inhibitory effect on the bone marrow red blood cells of mice and no mutagenic or distortion-inducing effects on the bone marrow cell chromosomes or spermatogonia chromosomes, so it is safe to eat. SOV can improve blood lipids and reduce blood lipid content. The study results provide data basis for the intensive processing of sugarcane and the development of high-value SOV products. Sugarcane original vinegar has a beneficial impact on performance, immune response, and chromosomal aberration. The production application influences the vinegar's quality and, consequently, its health benefits.

A gene-nutrient interaction between vitamin B6 and serine hydroxymethyltransferase (SHMT) affects genome integrity in Drosophila.

Pyridoxal 5'-phosphate (PLP), the catalytically active form of vitamin B6, participates as a cofactor to one carbon (1C) pathway that produces precursors for DNA metabolism. The concerted action of PLP-dependent serine hydroxymethyltransferase (SHMT) and thymidylate synthase (TS) leads to the biosynthesis of thymidylate (dTMP), which plays an essential function in DNA synthesis and repair. PLP deficiency causes chromosome aberrations (CABs) in Drosophila and human cells, rising the hypothesis that an altered 1C metabolism may be involved. To test this hypothesis, we used Drosophila as a model system and found, firstly, that in PLP deficient larvae SHMT activity is reduced by 40%. Second, we found that RNAi-induced SHMT depletion causes chromosome damage rescued by PLP supplementation and strongly exacerbated by PLP depletion. RNAi-induced TS depletion causes severe chromosome damage, but this is only slightly enhanced by PLP depletion. dTMP supplementation rescues CABs in both PLP-deficient and PLP-proficient SHMTRNAi . Altogether these data suggest that a reduction of SHMT activity caused by PLP deficiency contributes to chromosome damage by reducing dTMP biosynthesis. In addition, our work brings to light a gene-nutrient interaction between SHMT decreased activity and PLP deficiency impacting on genome stability that may be translated to humans.

Human papillomavirus associated XPF deficiency increases alternative end joining and cisplatin sensitivity in head and neck squamous cell carcinoma

ObjectivesHuman papillomavirus (HPV) positive head and neck squamous cell carcinoma (HNSCC) showed a considerably better prognosis with greater cisplatin sensitivity compared to their HPV-negative counterparts. Deciphering the underlying molecular mechanisms for HPV-induced cisplatin sensitivity is imperative to improve the prognosis of HPV-negative HNSCC. Materials and MethodsThe Fanconi anemia (FA) pathway status in HNSCC cells was analysed by detecting the cell cycle and chromosomal aberrations. XPF expression was validated using PCR, western blot, and immunohistochemistry. Droplet digital PCR and GFP expressing reporter assay were used to analyse the changes in alternative end-joining (alt-EJ) levels. The cisplatin sensitization was verified by cell proliferation assay, clonogenic cell survival assay, and TUNEL. ResultsHPV-positive HNSCC cells showed significant prolonged G2-M cell cycle arrest and aberrant chromosome formation under interstrand crosslinker treatment. Both mRNA and protein expression of XPF were considerably decreased in HPV-positive HNSCC, according to the analysis of cellular and clinical data. XPF inhibition upregulated the activity of the alt-EJ pathway in HPV-negative HNSCC cells by 32.02% (P < 0.001) but had little effect on HPV-positive HNSCC. Consistent with this, simultaneous suppression of XPF and alt-EJ enhanced cisplatin sensitivity of HPV-negative HNSCC in vitro and in vivo. ConclusionHPV-positive HNSCC cells exhibit a profound FA pathway deficiency associated with reduced XPF expression. HNSCC cells with compromised XPF function are more reliant on the alt-EJ pathway for genomic stability. Combining FA and alt-EJ inhibition may be used to cope with the hard-to-treat HPV-negative HNSCC.

General toxicity and genotoxicity studies of a new scale inhibitor for seawater desalination

Maleic acid polymer scale inhibitor is a new domestic seawater desalination scale inhibitor. This study tested the acute oral toxicity, sub-chronic toxicity and genotoxicity of this new inhibitor. The LD50 obtained from the acute oral toxicity test was 6810 and 9260 mg/kg·BW for male and female rats, as well as 1/5, 1/10 and 1/20 LD50 were as the dose for sub-chronic toxicity test. It showed the weight of male rats with high dose was significantly lower than the control group during the exposure period (p < 0.05), and the food consumption in the first 4 weeks was lower than the control group (p_week1 = 0.0261, p_week4 = 0.00222). The blood biochemical results showed the UREA in the medium- and high-dose groups were significantly higher than the control group (p_ female medium = 0.0047, p_high = 0.0037; p_male medium = 0.0026, p_high < 0.001), and increased as a dose dependence. Based on UREA results, the NOAEL and LOAEL were 1/20 LD50 and 1/10 LD50, respectively (males: 340.5 and 681 mg/kg·BW, females: 436 and 926 mg/kg·BW). Comet assay in vitro and Mammalian Erythrocyte Micronucleus Test were jointly to judge genotoxicity. This inhibitor did not cause chromosome aberrations in mouse bone marrow cells. However, the tail moment of CHO cell in all groups (p < 0.01) and the DNA% in tail in the 1/4 IC50 and IC50 groups were higher than the negative control (p < 0.001) in comet assay, suggesting the potential DNA damage in CHO cell. The oral LD50 and the NOAEL and LOAEL obtained in this study provides a theoretical basis for further toxicity research and risk assessment.Graphical

Cytogenetic Effects Of Fumagillin On Male Mice (Mus musculus)

The cytogenetic effects of Fumagillin were evaluated according to Mitotic Index (M.I) and aberration of metaphase chromosomes in bone marrow cells(CA) of white mice. The fumagillin was given as repeated oral gavages for 7 successive days after preparing the doses 10,15 at concentrations 20 mg/kg.b.wt. in 50% of sugar syrup . The positive control was given single I.p. dose of 20 mg/kg.b.wt. of methotrexate. The three dosages 10, 15, and 20 mg/kg.b.wt of Fumagillin induced significant decrease in mitotic index (3.90 ± 0.29, 3.60 ± 1.80, and 2.90 ±0.18) respectively compared with (7.10 ±0.29) for negative control. The results showed that the two dosages 15 and 20 mg/kg.b.wt of Fumagillin induced significant increase in the frequency of the chromosome aberration in bone marrow cells of the mice in the these groups (9.00± 0.92, 17.20 ± 1.42) respectively compared with (6.00 ±0.83) for negative control. The obtained result revealed the genetic and cellular toxic reaction of Fumagillin within the high and medium limits studied doses.

A Mission to Mars: Prediction of GCR Doses and Comparison with Astronaut Dose Limits.

Long-term human space missions such as a future journey to Mars could be characterized by several hazards, among which radiation is one the highest-priority problems for astronaut health. In this work, exploiting a pre-existing interface between the BIANCA biophysical model and the FLUKA Monte Carlo transport code, a study was performed to calculate astronaut absorbed doses and equivalent doses following GCR exposure under different shielding conditions. More specifically, the interface with BIANCA allowed us to calculate both the RBE for cell survival, which is related to non-cancer effects, and that for chromosome aberrations, related to the induction of stochastic effects, including cancer. The results were then compared with cancer and non-cancer astronaut dose limits. Concerning the stochastic effects, the equivalent doses calculated by multiplying the absorbed dose by the RBE for chromosome aberrations ("high-dose method") were similar to those calculated using the Q-values recommended by ICRP. For a 650-day mission at solar minimum (representative of a possible Mars mission scenario), the obtained values are always lower than the career limit recommended by ICRP (1 Sv), but higher than the limit of 600 mSv recently adopted by NASA. The comparison with the JAXA limits is more complex, since they are age and sex dependent. Concerning the deterministic limits, even for a 650-day mission at solar minimum, the values obtained by multiplying the absorbed dose by the RBE for cell survival are largely below the limits established by the various space agencies. Following this work, BIANCA, interfaced with an MC transport code such as FLUKA, can now predict RBE values for cell death and chromosome aberrations following GCR exposure. More generally, both at solar minimum and at solar maximum, shielding of 10 g/cm2 Al seems to be a better choice than 20 g/cm2 for astronaut protection against GCR.

Genotoxic and mutagenic potential of 7-methylxanthine: an investigational drug molecule for the treatment of myopia

7-Methylxanthine (7-MX, CAS No. 552-62-5, purity 99.46%) is the first orally administered drug candidate, which showed anti-myopic activity in different pre-clinical studies. In the present study, we investigated the in-vivo genotoxic and mutagenic toxicity of 7-MX in Wistar rats using comet/single-cell gel electrophoresis, chromosomal aberration and micronucleus assays after oral administration. For the single-dose study (72 h), two doses of 7-MX 300 and 2000 mg/kg body weight were selected. For a repeated dose 28 d study, three doses (250, 500, and 1000 mg/kg) of 7-MX were selected. The doses were administered via oral gavage in the suspension form. Blood and major vital organs such as bone marrow, lung and liver were used to perform comet/single cell gel electrophoresis, chromosomal aberration, and micronucleus assays. The in-vitro Ames test was performed on TA98 and TA100 strains. In the chromosomal aberration study, a non-significant increase in deformities such as stickiness, ring chromosome, and endoreduplication was observed in bone marrow cells of 7-MX treated groups. These chromosomal alterations were observed upon treatment with doses of 2000 mg/kg single dose for 72 h and 1000 mg/kg repeated dose for 28 d. At a dose of 500 mg/kg, DNA damage in terms of tail length, tail moment, % tail DNA and the olive tail moment was also found to be non-significant in 7-MX treated groups. The Ames test showed the non-mutagenic nature of 7-MX in both strains of TA98 and TA100 of Salmonella typhimurium with or without metabolic activation. Thus, the present work is interesting in view of the non- genotoxicity and non-mutagenicity of repeated doses of 7-MX.

Ectopic expression of HIV-1 Tat modifies gene expression in cultured B cells: implications for the development of B-cell lymphomas in HIV-1-infected patients.

An increased frequency of B-cell lymphomas is observed in human immunodeficiency virus-1 (HIV-1)-infected patients, although HIV-1 does not infect B cells. Development of B-cell lymphomas may be potentially due to the action of the HIV-1 Tat protein, which is actively released from HIV-1-infected cells, on uninfected B cells. The exact mechanism of Tat-induced B-cell lymphomagenesis has not yet been precisely identified. Here, we ectopically expressed either Tat or its TatC22G mutant devoid of transactivation activity in the RPMI 8866 lymphoblastoid B cell line and performed a genome-wide analysis of host gene expression. Stable expression of both Tat and TatC22G led to substantial modifications of the host transcriptome, including pronounced changes in antiviral response and cell cycle pathways. We did not find any strong action of Tat on cell proliferation, but during prolonged culturing, Tat-expressing cells were displaced by non-expressing cells, indicating that Tat expression slightly inhibited cell growth. We also found an increased frequency of chromosome aberrations in cells expressing Tat. Thus, Tat can modify gene expression in cultured B cells, leading to subtle modifications in cellular growth and chromosome instability, which could promote lymphomagenesis over time.

Acute, chronic, and genotoxic studies on the protopine total alkaloids of the Macleaya cordata (willd.) R. Br. in rodents.

The protopine alkaloids are widely distributed within the opium poppy family and have a wide range of pharmacological effects. MPTA is a product of the protopine total alkaloids extracted from the Macleaya cordata (Willd.) R. Br. Previously, we reported good anti-inflammatory activity of MPTA as well as oral acute and sub-chronic toxicity studies in rats. In order to perform a systematic toxicological safety assessment of MPTA, oral acute toxicity, genotoxicity (bone marrow cell chromosome aberration test, sperm abnormality test, bone marrow cell micronucleus test, and rat teratogenicity test), and chronic toxicity in mice were performed in this study. In the oral acute toxicity test, the LD50 in ICR mice was 481.99 mg/kg, with 95% confidence limits ranging from 404.27 to 574.70 mg/kg. All three mutagenicity tests tested negative in the range of 60.25–241.00 mg/kg. The results of the teratogenicity test in rats showed no reproductive or embryonic developmental toxicity at only 7.53 mg/kg, which can be considered as a no observed effect level (NOEL) for the teratogenicity test. Therefore, MPTA is safe for use at the doses tested, but attention should be paid to the potential risk to pregnant animals and the safety evaluation and toxicity mechanisms in target animals should be further investigated.

Protective effect of zinc complex with hypoxanthine-9-riboside on wheat seedlings grown from gamma-irradiated seeds

Aim. The aim of the research was to obtain the zinc complex hypoxanthine-9-riboside and to study its effect during γ-irradiation on the biosynthesis of chlorophylls, carotenoids and on the release of chromosome aberrations in anaphase root hair cells in wheat seedlings. Methods. The zinc complex was obtained by direct interaction of zinc chloride – ZnCl2 with hypoxanthine-9-riboside. X-ray phase analysis and thermogravimetric measurements of the obtained complex were carried out. Before irradiation, seeds of durum wheat Triticum durum L. from a 60Co source were treated with a zinc complex with hypoxanthine-9-riboside at concentrations of 0.1; 0.01; 0.001%. Structural changes in chromosomes were determined in the initial and final stages of anaphase. Determination of chlorophylls and carotenoids was carried out according to Shlyk. Results. g-irradiation at doses of 50, 100 and 200 Gy has a significant effect on the content of green pigments and carotenoids in wheat seedlings. Under the action of g-irradiation, the content of chlorophyll decreases more than carotenoids. With an increase in the dose of radiation, a slight increase in the content of carotenoids is noted. In all variants, chromosomal abnormalities were found: the formation of fragments in metaphase and anaphase, bridges in anaphase, chromosome delays, uneven division of chromosomes. Conclusions. For the first time, it was found that the Zn (II) complex of hypoxanthine-9-riboside at the indicated concentrations significantly reduces the damaging effect of γ-irradiation, helps to eliminate abnormalities in mitotic division in wheat root hair cells.

Comparison of biological measurement and physical estimates of space radiation in the International Space Station

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.

Oxidative stress in metabolic diseases: current scenario and therapeutic relevance.

The metabolic syndrome is a clustering condition of increased abdominal obesity in concert with hyperglycemia, insulin resistance, hypertension, and dyslipidemia. It confers higher risk of metabolic diseases such as diabetes and ischemic heart disease and has been observed to be associated with high morbidity and mortality. It is a progressive pathological process for diabetes-induced complications and appears to be multifactorial in origin. Several preclinical, clinical, and epidemiological reports have shown a persistent link between the metabolic syndrome and oxidative stress. There is pronounced imbalance between pro-oxidants and anti-oxidants with increased production of oxidizing molecules, depletion of anti-oxidants, and consequently accumulation of protein and lipid oxidation products in the cell in metabolic syndrome. The increased cellular pro-oxidant activity also results in altered molecular pathways, mitochondrial dysfunction, deregulation in cell cycle control, chromosomal aberrations, inflammation, and overall decreased biological activity as well as impairment of the antioxidant systems. Here, the focus of our review article will be on the formation of oxidative species, the interplay between metabolic syndrome and oxidative stress, and its potential implications in therapeutic approaches.

Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the Drosophila warts (wts) Locus

The active form of vitamin B6, pyridoxal 5′-phosphate (PLP), is a cofactor for more than 200 enzymes involved in many metabolic pathways. Moreover, PLP has antioxidant properties and quenches the reactive oxygen species (ROS). Accordingly, PLP deficiency causes chromosome aberrations in Drosophila, yeast, and human cells. In this work, we investigated whether PLP depletion can also cause loss of heterozygosity (LOH) of the tumor suppressor warts (wts) in Drosophila. LOH is usually initiated by DNA breakage in heterozygous cells for a tumor suppressor mutation and can contribute to oncogenesis inducing the loss of the wild-type allele. LOH at the wts locus results in epithelial wts homozygous tumors easily detectable on adult fly cuticle. Here, we found that PLP depletion, induced by two PLP inhibitors, promotes LOH of wts locus producing significant frequencies of wts tumors (~7% vs. 2.3%). In addition, we identified the mitotic recombination as a possible mechanism through which PLP deficiency induces LOH. Moreover, LOH of wts locus, induced by PLP inhibitors, was rescued by PLP supplementation. These data further confirm the role of PLP in genome integrity maintenance and indicate that vitamin B6 deficiency may impact on cancer also by promoting LOH.

First application of the BIANCA biophysical model to carbon-ion patient cases

Objective. The main objective of this work consists of applying, for the first time, the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model to the RBE calculation for C-ion cancer patients, and comparing the outcomes with those obtained by the LEM I model, which is applied in clinics. Indeed, the continuous development of heavy-ion cancer therapy requires modelling of biological effects of ion beams on tumours and normal tissues. The relative biological effectiveness (RBE) of heavy ions is higher than that of protons, with a significant variation along the beam path. Therefore, it requires a precise modelling, especially for the pencil-beam scanning technique. Currently, two radiobiological models, LEM I and MKM, are in use for heavy ions in scanned pencil-beam facilities. Approach. Utilizing an interface with the FLUKA Particle Therapy Tool, BIANCA was applied to re-calculate the RBE-weighted dose distribution for carbon-ion treatment of three patients (chordoma, head-and-neck and prostate) previously irradiated at CNAO, where radiobiological optimization was based on LEM I. The predictions obtained by BIANCA were based either on chordoma cell survival (RBE surv ), or on dicentric aberrations in peripheral blood lymphocytes (RBE ab ), which are indicators of late normal tissue damage, including secondary tumours. The simulation outcomes were then compared with those provided by LEM I. Main results. While in the target and in the entrance channel BIANCA predictions were lower than those obtained by LEM I, the two models provided very similar results in the considered OAR. The observed differences between RBE surv and RBE ab (which were also dependent on fractional dose and LET) suggest that in normal tissues the information on cell survival should be integrated by information more closely related to the induction of late damage, such as chromosome aberrations. Significance. This work showed that BIANCA is suitable for treatment plan optimization in ion-beam therapy, especially considering that it can predict both cell survival and chromosome aberrations and has previously shown good agreement with carbon-ion experimental data.

Evaluation of Genotoxic Effect of Phloxine by Allium Test

Phloxine is used as a food dye. In this study, genotoxicity of phloxine at the root tip of Allium cepa L. was investigated. A. cepa L. meristematic root tip cells were treated with ten different doses of phloxine. In this way, the EC50 value was determined. Then, phloxine was applied to root tips at EC50/2, EC50 and EC50×2 doses. Treatment time was determined as 24, 48 and 72 hours. As a result, it was revealed that phloxine caused chromosomal aberrations in cells in mitotic cycle at the root tip of A. cepa. There are equatorial plate shifting in metaphase, laggard chromosome, disturbed spindle, chromosome stickiness, C-mitosis, polar shifting among the observed chromosomal aberrations. It was stated that the % chromosomal aberration index (CAI) increased depending on concentration increase. It has been demonstrated that the highest % chromosomal aberration index occurred at the EC50×2 dose for 72 hours. According to the research, it was revealed that phloxine has a genotoxic effect on the root cells of A. cepa. For this reason, it can be emphasized that care should be taken in its use in foods.

Radiobiological damage by space radiation: extension of the BIANCA model to heavy ions up to iron, and pilot application to cosmic ray exposure

Space research seems to be object of a renewed interest, also considering that human missions to the Moon, and possibly Mars, are being planned. Among the risks affecting such missions, astronauts’ exposure to space radiation is a major concern. In this work, the question of the evaluation of biological damage by Galactic Cosmic Rays (GCR) was addressed by a biophysical model called BIophysical ANalysis of Cell death and chromosome Aberrations (BIANCA), which simulates the induction of cell death and chromosome aberrations by different ions. While previously BIANCA has been validated for calculating cell death along hadrontherapy beams up to oxygen, herein the approach was extended up to Fe ions. Specifically, experimental survival curves available in literature for V79 cells irradiated by Si-, Ne-, Ar- and Fe-ions were reproduced, and a reference radiobiological database describing V79 cell survival as a function of ion type (1 ⩽ Z ⩽ 26), energy and dose was constructed. Analogous databases were generated for Chinese hamster ovary hamster cells and human skin fibroblasts, finding good agreement between simulations and data. Concerning chromosome aberrations, which are regarded as radiation risk biomarkers, dicentric data in human lymphocytes irradiated by heavy ions up to iron were reproduced, and a radiobiological database allowing calculation of lymphocyte dicentric yields as a function of dose, ion type (1 ⩽ Z ⩽ 26) and energy was constructed. Following interface between BIANCA and the FLUKA Monte Carlo transport code, a feasibility study was performed to calculate the relative biological effectiveness (RBE) of different GCR spectrum components, for both dicentrics and cell death. Fe-ions, although representing only 10% of the total absorbed dose, were found to be responsible for about 35%–40% of the RBE-weighted dose. Interestingly, the RBE for dicentrics was higher than that for cell survival. More generally, this work shows that BIANCA can calculate RBE values for cell death and lymphocyte dicentrics not only for ion therapy, but also for space radiation.

Gamma Irradiation Induced Chromosome Aberrations in Meiotic Cells of Bread Wheat (Triticum aestivum L.)

Background and Objectives: Due to the ever-increasing human population and rapid urbanization, the available agricultural land becomes limited for the production of food grains. As a result, there is an urgent need for creating genetic variability upon which improved varieties could be made. The technology of induced mutagenesis plays an essential role in inducing genetic variations among crop species where hybridization is very challenging. Therefore, the present study has been designed to assess the mutagenic impact of gamma irradiation on the cytological behaviour of T. aestivum L in M1 and M2 generation.&#x0D; Materials and Methods: Bread wheat seeds of selected cultivar were irradiated at BARC, Mumbai with five doses. The irradiated and non-irradiated seeds were sown under field condition with three replicates for each dose according to randomized block design to raise the M1 and M2 generations for morphological and meiotic analysis. For meiosis, immature panicles were collected in early morning and immediately fixed in carnoy’s solution for at least 24 hours. Thereafter, anthers from buds were excised and squashed in acetocarmine followed by photomicrography of suitable PMCs to estimate chromosome aberrations.&#x0D; Results: The results displayed a progressive elevation in the chromosomal aberrations along with a significant influence on seedling emergence, plant survival and pollen fertility. The most frequent meiotic aberrations detected include chromatin clumping, univalents and early chromosome segregations at metaphase and lagging chromosomes, chromatin bridges and chromosome clumping at anaphase/telophase while unorientation, scattering, polarity disturbances and micronuclei were also noticed. In addition, the frequency of these chromosome aberrations significantly decreased in M2 generation depicting the reclamation in genomic structure.&#x0D; Conclusion: The present investigation supports the discovery that gamma irradiations are very effective in creating rapid genetic variability in crop plants including Triticum aestivum which could be essentially exploited for future mutation breeding programmes. The results revealed that the higher treatment doses are toxic whereas lower doses of gamma irradiations seem quite beneficial in generating promising traits with less toxicity. In this study, the cytotoxicity has increased along with gamma irradiation doses and therefore, the genetic structure of the selected bread wheat cultivar is highly affected, which will possibly create new favorable genetic changes in the following generations that would be useful for plant breeders for its improvement.

Toxicological and safety evaluations of Weissella cibaria strain CMU in animal toxicity and genotoxicity

Weissella cibaria belongs to the Lactobacillaceae family and has been isolated from traditional fermented foods and saliva of children with good oral health. Previous investigations have shown that W. cibaria CMU (Chonnam Medical University) is expected to be safe based on results of in silico and in vitro analyses. However, there is a lack of studies assessing its safety in vivo. A toxicological safety evaluation of W. cibaria CMU was performed using an acute oral safety study in rats, a 14-day oral range finding study, a subsequent 13-week oral toxicity study in rats and a genetic toxicity battery (in vitro bacterial reverse mutation, in vitro chromosome aberration in Chinese Hamster Ovary cells and in vivo micronucleus study in mice). The results of the studies in rats showed that the acute lethal dose of W. cibaria CMU is > 5000 mg/kg body weight (bw)/day (1.8 × 109 CFU/kg bw/day) and the 14-day or 13-week no observed adverse effect level (NOAEL) is 5000 mg/kg bw/day (1.8 × 109 CFU/kg bw/day), the highest dose administered. W. cibaria CMU was non-mutagenic in the bacterial reverse mutation test and non-clastogenic or aneugenic in vitro and in vivo. In conclusion, the toxicological studies performed demonstrated W. cibaria CMU to be a safe strain to consume. This study is the first study examining the potential of a W. cibaria strain to cause genetic toxicity and subchronic toxicity in rats according to the Organization for Economic Cooperation and Development guidelines.