Role of L-Ornithine in Mitigation of Salt Stress In Allium Cepa L.

Effects of L-ornithine (150 mg/l) on the germination, seedling growth, mitotic index, chromosome aberrations and micronucleus frequency of Allium cepa L. bulbs germinated at 0.125 M salinity were studied. The radicle number of the group III bulbs germinated in the medium with ornithine alone as compared to ones of the group I (control) bulbs which germinated in distilled water medium. But, their germination percentage, radicle length and fresh weight were statistically the same as ones of the group I bulbs. Besides, the micronucleus frequency and chromosomal abnormalities in the root-tip meristematic cells of the group III bulbs showed increased germination compared to ones of the group I bulbs. However, their mitotic index statistically showed the same value as the group I bulbs. Salt stress significantly inhibited the germination and seedling growth of A. cepa bulbs. Moreover, it reduced the mitotic index in the root-meristem cells of the bulbs and fairly increased the number of chromosome aberrations and micronucleus frequency. On the other hand, the inhibitive effect of salt on the germination, seedling growth, mitotic index and micronucleus frequency was dramatically alleviated in varying degrees by ornithine application. But, it was ineffective in reducing the detrimental effect of salinity on the chromosome aberrations. The germination percentage, radicle lenght, radicle number, fresh weight, mitotic index, micronucleus frequency and chromosomal aberrations of the group II seedlings grown in 0.125 M salinity were 27%, 13.5 mm, 18.4, 7.1 g, 5.5, 18.3 and 60.8%, respectively while these values became 68%, 16.4 mm, 16.4, 10.5 g, 15.6, 7.6 and 74.8% in the group IV seedlings treated with L-ornithine. Bangladesh J. Bot. 50(4): 1165-1171, 2021 (December)

Retrospective Analysis of INRG Clinical and Genomic Factors for 605 Neuroblastomas in Japan: A Report from the Japan Children’s Cancer Group Neuroblastoma Committee (JCCG-JNBSG)

Neuroblastomas (NBs) exhibit broad and divergent clinical behaviors and tumor risk classification at diagnosis is crucial for the selection of an appropriate therapeutic strategy for each patient. The present study aimed to validate the clinical relevance of International Neuroblastoma Risk Group (INRG) prognostic and genomic markers in a Japanese NB cohort using a retrospective analysis. Follow-up data based on 30 common INRG queries in 605 NB cases diagnosed in Japan between 1990 and 2014 were collected and the genome signature of each tumor sample was integrated. As previously indicated, age, tumor stage, MYCN, DNA ploidy, the adrenals as the primary tumor site, serum ferritin and lactate dehydrogenase (LDH) levels, segmental chromosome aberrations, and the number of chromosome breakpoints (BP) correlated with lower survival rates, while the thorax as the primary tumor site and numerical chromosome aberrations correlated with a favorable prognosis. In the patient group with stage 4, MYCN non-amplified tumors (n = 225), one of the challenging subsets for risk stratification, age ≥ 18 months, LDH ≥ 1400 U/L, and BP ≥ 7 correlated with lower overall and event-free survival rates (p < 0.05). The genome subgroup GG-P2s (partial chromosome gain/loss type with 1p/11q losses and 17q gain, n = 30) was strongly associated with a lower overall survival rate (5-year survival rate: 34%, p < 0.05). Therefore, the combination of the tumor genomic pattern (GG-P2s and BP ≥ 7) with age at diagnosis and LDH will be a promising predictor for MYCN-non-amplified high-risk NBs in patient subsets, in accordance with previous findings from the INRG project.

Summary of four scientific studies on Arsenicum album high dilution effect against Arsenic intoxication in mice

Background: Groundwater arsenic affects millions of people in about 20 countries. In West Bengal (India) and Bangladesh alone over 100 million people are exposed. The arsenic concentration in contaminated groundwater in Bangladesh was above the maximum permissible level of 0.05 mg/l as recommended by WHO for developing countries [1]. Drinking water is not the only source of poisoning. In arsenic contaminated areas, crops, vegetables, cereals, poultry, cattle, etc, also contain traces of arsenic. Chronic arsenic intoxication has been associated with several diseases such as melanosis, leuco-melanosis, hyperkeratosis, oedema, skin cancer… Cazin et al [2], have demonstrated the effect of high dilutions of arsenic compounds. They noted increased arsenic elimination from blood through urine and faeces in intoxicated rats. According to these research, the aim of Khuda Buksh studies [3-4-5] was to investigate whether high dilution Arsenicum album have any effect on arsenic accumulation in different tissues and to understand also how this high dilution could produce a protective effect on all the different organs. Methodology: Firstly, the effect of Arsenicum album 30 cH on the amount of arsenic accumulation was determined by spectrophotometric analysis in four tissues namely liver, kidney and testis in mice intoxicated by arsenic. The protective effect in chronic and acute arsenic intoxicated mice of Arsenicum Album 6cH, 30cH and 200cH has been evaluated using not only the activities of enzymatic and biomarker toxicity (aspartate amino transferase (AST), alanine amino transferase (ALT), acid phosphatase (AcP), alkaline phosphatase (AlkP), lipid peroxidation (LPO) and reduced glutathione (GSH)) but also the cytogenetical parameters (chromosome aberrations (CA), mitotic index (MI), sperm head anomaly (SHA) etc., ). Because, it is well demonstrated that these enzymes biomarkers reflect the degree of hepatotoxicity and oxidative stress caused by arsenic intoxication. Results: Compared to controls, Arsenicum album 30cH induced a significant decrease in accumulation of arsenic in 4 tissues namely liver, spleen, kidney and testis in intoxicated mice. In addition, both Arsenicum album 6cH, 30cH and 200cH reduced chromosome aberrations, sperm head abnormality frequencies and activities of acid and alkaline phosphatases, aspartate and alanine aminotransferases and lipid peroxidation, while mitotic index and activities of glutathione, catalase and succinate dehydrogenase were increased compared to controls. Conclusion: Altogether, theses results provide evidence of protective potentials of the Arsenicum album dilution against acute and chronic arsenic intoxication in mice. They also offer a new hypothesis that the mechanism of the homeopathic dilution could act through regulation of expression of certain genes. This explanation seems to be plausible because all biomarker tests are regulated by specific genetic regulatory mechanisms [6]. keywords: Arsenicum album, arsenic intoxication, enzymatic and biomarker toxicity. References: [1] WHO. WHO Guidelines for Drinking Water Quality, Vol. 2, 2nd edition. Geneva: WHO, 1996, 940–9. [2] Cazin JC, Cazin M, Gaborit JL, Chaoui A, Boiron J, Belon P, et al. A study of the effect of decimal and centesimal dilutions of arsenic on the retention and mobilization of arsenic in the rat. Hum Toxicol 1987;6:315–20. [3] Mitra K, Kundu SN, Khuda-Bukhsh AR. Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing toxic effects produced by of arsenic trioxide in mice. I. On rate accumulation of arsenic in certain vital organs. Comp Ther Med 1998;6:178–84. [4] Pathikrit Banerjee. Evidences of Protective Potentials of Microdoses of Ultra-high Diluted Arsenic Trioxide in Mice Receiving Repeated Injections of Arsenic Trioxide. eCAM 2009; 1-10. [5] Pathikrit Banerjee, Comparative Efficacy of Two Microdoses of a Potentized Homeopathic Drug, Arsenicum Album, to Ameliorate Toxicity Induced by Repeated Sublethal Injections of Arsenic Trioxide in Mice. Pathobiology 2008;75:156–170. [6]/ Khuda-Bukhsh AR. Potentized homeopathic drugs act through regulation of gene expression: a hypothesis to explain their mechanism and pathways of action in vivo. Comp Ther Med 1997;5:43–6

Metaphase-Based Cytogenetic Approach Identifies Radiation-Induced Chromosome and Chromatid Aberrations in Zebrafish Embryos

Metaphase-based cytogenetic methods based on scoring of chromosome aberrations for the estimation of the radiation dose received provide a powerful approach for evaluating the associated risk upon radiation exposure and form the bulk of our current knowledge of radiation-induced chromosome damages. They mainly rely on inducing quiescent peripheral lymphocytes into proliferation and blocking them at metaphases to quantify the damages at the chromosome level. However, human organs and tissues demonstrate various sensitivity towards radiation and within them, self-proliferating progenitor/stem cells are believed to be the most sensitive populations. The radiation-induced chromosome aberrations in these cells remain largely unknown, especially in the context of an intact living organism. Zebrafish is an ideal animal model for research into this aspect due to their small size and the large quantities of progenitor cells present during the embryonic stages. In this study, we employ a novel metaphase-based cytogenetic approach on zebrafish embryos and demonstrate that chromosome-type and chromatid-type aberrations could be identified in progenitor cells at different cell-cycle stages at the point of radiation exposure. Our work positions zebrafish at the forefront as a useful animal model for studying radiation-induced chromosome structural changes in vivo.

Cr and Ni simultaneous phytotoxicity and mutagenicity assay

For genotoxicity study simultaneous phytotoxicity and mutagenicity assay with Vicia sativa L. var. Klára was used. For phytotoxicity the following rank orders of growth inhibition can be arranged: for roots: Ni(II) > Cr(VI) > Cr(III); for shoots: Ni(II) > Cr(VI) ≥ Cr (III). For mutagenicity assay root tips of V. sativa were used and chromosome aberrations were determined at least in 500-anatelophases. All tested metals exerted in V. sativa a significant increase of chromosomal aberration rate in applied concentrations. Maximum of aberrations invoked Cr(VI) and the rank order of aberrations fall was: Cr(VI) > Ni(II) > Cr(III). Genotoxic effects of metals were determined by analysis of micronuclei frequency in the pollen tetrads of Tradescantia plants. None of tested metal significantly stimulated micronuclei frequency and genotoxic effect was decreased in order: Cr(VI) ≥ Ni(II) > Cr(III).

The Effects of 1-Beta-D-Arabinofuranosylcytosine and Adriamycin on the Chromosomes of Cultured Human Lymphocytes

<p>A study of chromosome aberrations induced by 1-Beta-D-arabinofuranosylcytosine (Ara C) and Adriamycin (AM) in the chromosomes of cultured human lymphocytes was made. There were significant increases in the frequency of aberrations with increasing concentrations of both Ara C (2.5, 5.0 and 10.0 mug/ml) and AM (0.01, 0.05, 0.10 and 0.15 mug/ml). The frequency of aberrations induced by both drugs also showed a 'levelling off' above particular concentrations. For Ara C the effect of increasing treatment time was also studied. The frequency of aberrations increased significantly with increasing treatment times (2, 3 and 4 hrs) although no 'levelling off' in the number of aberrations was observed. The relationship between the frequency of the different types of aberrations induced by Ara C and AM was studied. AM allowed for a study of the relative frequency of chromosome versus chromatid aberrations and fragment versus exchange aberrations. There were always more fragments than exchanges, and always more chromatid aberrations than chromosome aberrations. Aberrations induced by Ara C were all of the chromatid fragment type. A study was made of the distribution of inter- and intra-chromosomal aberrations in relation to light and dark G banded chromosomes. Both drugs induced more aberrations in the light G bands than the dark G bands. Both drugs showed distinct clustering of aberrations in some regions of the chromosomes (hotspots), although the location of AM induced hotspots was different from the location of those induced by Ara C. The distribution of AM induced chromatid aberrations was different from the distribution of the chromosome aberrations, as were the distributions of the fragment and exchange aberrations. The different types of aberrations also differed in the number of AM induced aberrations per unit length between the p and q arms. There were more aberrations per unit length in the p arm than in the q arm for exchanges, whereas for fragments and chromosome aberrations the reverse was true. For chromatid aberrations, there was no significant difference in the number of aberrations per unit length between the p and q arms. Inter-individual differences in the frequency of AM induced aberrations were observed in the .AM dosage experiments. Also there was a suggestion that the distribution of Ara C induced aberrations was different for different donors. AM increased the frequency of sister chromatid exchanges. Comparable results were not sought for Ara C because after cells were exposed to Ara C they did not pass through an S phase of the cell cycle, as is the case for cells exposed to AM. The relevance of the present in vitro studies to cancer chemotherapy is briefly discussed.</p>

The Effects of 1-Beta-D-Arabinofuranosylcytosine and Adriamycin on the Chromosomes of Cultured Human Lymphocytes

<p>A study of chromosome aberrations induced by 1-Beta-D-arabinofuranosylcytosine (Ara C) and Adriamycin (AM) in the chromosomes of cultured human lymphocytes was made. There were significant increases in the frequency of aberrations with increasing concentrations of both Ara C (2.5, 5.0 and 10.0 mug/ml) and AM (0.01, 0.05, 0.10 and 0.15 mug/ml). The frequency of aberrations induced by both drugs also showed a 'levelling off' above particular concentrations. For Ara C the effect of increasing treatment time was also studied. The frequency of aberrations increased significantly with increasing treatment times (2, 3 and 4 hrs) although no 'levelling off' in the number of aberrations was observed. The relationship between the frequency of the different types of aberrations induced by Ara C and AM was studied. AM allowed for a study of the relative frequency of chromosome versus chromatid aberrations and fragment versus exchange aberrations. There were always more fragments than exchanges, and always more chromatid aberrations than chromosome aberrations. Aberrations induced by Ara C were all of the chromatid fragment type. A study was made of the distribution of inter- and intra-chromosomal aberrations in relation to light and dark G banded chromosomes. Both drugs induced more aberrations in the light G bands than the dark G bands. Both drugs showed distinct clustering of aberrations in some regions of the chromosomes (hotspots), although the location of AM induced hotspots was different from the location of those induced by Ara C. The distribution of AM induced chromatid aberrations was different from the distribution of the chromosome aberrations, as were the distributions of the fragment and exchange aberrations. The different types of aberrations also differed in the number of AM induced aberrations per unit length between the p and q arms. There were more aberrations per unit length in the p arm than in the q arm for exchanges, whereas for fragments and chromosome aberrations the reverse was true. For chromatid aberrations, there was no significant difference in the number of aberrations per unit length between the p and q arms. Inter-individual differences in the frequency of AM induced aberrations were observed in the .AM dosage experiments. Also there was a suggestion that the distribution of Ara C induced aberrations was different for different donors. AM increased the frequency of sister chromatid exchanges. Comparable results were not sought for Ara C because after cells were exposed to Ara C they did not pass through an S phase of the cell cycle, as is the case for cells exposed to AM. The relevance of the present in vitro studies to cancer chemotherapy is briefly discussed.</p>

Association of X Chromosome Aberrations with Male Infertility

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.

Chromosome Aberrations in Lymphocytes of Patients Undergoing Radon Spa Therapy: An Explorative mFISH Study

In the present exploratory study, we aim to elucidate the action of radon in vivo and to assess the possible health risks. Chromosome aberrations were analyzed in lymphocytes of two patients (P1, P2) undergoing radon spa therapy in Bad Steben (Germany). Both patients, suffering from painful chronic degenerative disorders of the spine and joints, received nine baths (1.2 kBq/L at 34 °C) over a 3-week period. Chromosome aberrations were analyzed before and 6, 12 and 30 weeks after the start of therapy using the high-resolution multiplex fluorescence in situ hybridization (mFISH) technique. For comparison, the lymphocytes from two healthy donors (HD1, HD2) were examined. P1 had a higher baseline aberration frequency than P2 and both healthy donors (5.3 ± 1.3 vs. 2.0 ± 0.8, 1.4 ± 0.3 and 1.1 ± 0.1 aberrations/100 analyzed metaphases, respectively). Complex aberrations, biomarkers of densely ionizing radiation, were found in P1, P2 and HD1. Neither the aberration frequency nor the fraction of complex aberrations increased after radon spa treatment, i.e., based on biological dosimetry, no increased health risk was found. It is worth noting that a detailed breakpoint analysis revealed potentially clonal aberrations in both patients. Altogether, our data show pronounced inter-individual differences with respect to the number and types of aberrations, complicating the risk analysis of low doses such as those received during radon therapy.

Healthy Tissue Damage Following Cancer Ion Therapy: A Radiobiological Database Predicting Lymphocyte Chromosome Aberrations Based on the BIANCA Biophysical Model

Chromosome aberrations are widely considered among the best biomarkers of radiation health risk due to their relationship with late cancer incidence. In particular, aberrations in peripheral blood lymphocytes (PBL) can be regarded as indicators of hematologic toxicity, which is a major limiting factor of radiotherapy total dose. In this framework, a radiobiological database describing the induction of PBL dicentrics as a function of ion type and energy was developed by means of the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model, which has been previously applied to predict the effectiveness of therapeutic-like ion beams at killing tumour cells. This database was then read by the FLUKA Monte Carlo transport code, thus allowing us to calculate the Relative Biological Effectiveness (RBE) for dicentric induction along therapeutic C-ion beams. A comparison with previous results showed that, while in the higher-dose regions (e.g., the Spread-Out Bragg Peak, SOBP), the RBE for dicentrics was lower than that for cell survival. In the lower-dose regions (e.g., the fragmentation tail), the opposite trend was observed. This work suggests that, at least for some irradiation scenarios, calculating the biological effectiveness of a hadrontherapy beam solely based on the RBE for cell survival may lead to an underestimation of the risk of (late) damage to healthy tissues. More generally, following this work, BIANCA has gained the capability of providing RBE predictions not only for cell killing, but also for healthy tissue damage.