Induction Of Chromosomal Aberrations Research Articles

Retrospective cytogenetic analysis of unstable and stable chromosome aberrations in the victims of radiation accident in Bulgaria

Five occupational workers in an industrial sterilization unit at Stamboliyski in Bulgaria were accidentally exposed to a very high specific activity of Cobalt-60 source on June 14, 2011. Initial cytogenetic analysis performed on days 2 and 7 after radiation exposure revealed the whole body absorbed radiation doses of 5.32 Gy for patient 1, 3.40 Gy for patient 2, 2.50 Gy for patient 3, 1.91 Gy for patient 4 and 1.24 Gy for patient 5 [1]. Here, a retrospective multicolor FISH analysis was performed on three patients (patients 1, 2 and 3) using the blood samples collected over a period of 4 years from 2012 through 2015. In all the three patients, cells with stable chromosome aberrations (simple and complex chromosome translocations) were 3–4 folds more than cells with unstable chromosome aberrations (dicentric, rings and excess acentric chromosome fragments). In corroboration with the results reported in the literature, we observed that the time dependent decline of dicentrics, rings and excess acentric fragments occurred much more rapidly than chromosome translocations in the blood samples of the three victims. Further, inter-individual variation in the decline of radiation induced chromosome aberrations was also noticed among the three victims. The reason for the increased persistence of balanced chromosome translocations is not entirely clear but may be attributed to certain subsets of long-lived T-lymphocytes. The retrospective cytogenetic follow up studies on radiation-exposed victims may be useful for determining the extent of genomic/chromosomal instability in the hematopoietic system.

Induction of chromosome aberrations in B14-150 cells following carbon ions irradiation at low doses

Dose-dependences of the chromosomal aberrations induction in B14-150 cells were studied for carbon ions (E ∼455 MeV/nucleon) with different values of the linear energy transfer (LET): 10-12 keV/μm (proximal region of the Bragg curve - plateau) and 25-27 keV/μm (tail of the Bragg curve). It is shown that the level of chromosome aberrations was higher for irradiation at tail of carbon beam. The dose relations were described by a modified linear-quadratic model and had a similar character in the studied dose range of 0.05-2.5 Gy. A sharp increase of the chromosome aberrations yield at the dose range up to 0.1 Gy (hyper-radiosensitivity, HRS), slowdown in it at the range of 0.1-0.3 Gy (induced radioresistance, IRR) and a further its’ growth above 0.3 Gy were observed with a transformation to linear and linear-quadratic dependences. The results obtained agree with the known literature data and indicates the likeness of the biological effect of hyper-radiosensitivity and induced radioresistance (HRS/IRR) for different cell lines.

Protective Effects of Ginger extract against Methotrexate induced cytotoxicity in mice

Ginger (Zingiber officinalis) is one of the frequently used spices in the world and medicinal plant, which has been used all over the world. This study was designed to investigate the role of aqueous ginger extract to inhibit the genotoxicity of methotrexate (MTX) in female albino mice by using these parameters: mitotic index (MI), chromosome aberrations (CA) and micronuclei formation (MNPCE) in somatic cells (bone marrow). The cytological protection of aqueous ginger extract (AGE) was performed at doses (25, 50) mg \\ kg against MTX effects (0.5) mg/kg for three weeks exposure. The results revealed the high inhibitory effects of MTX for cell division in addition to induction of chromosome aberration with micronuclei formation, the absence of cytotoxicity for AGE at tested doses, and the inhibitory efficiency of AGE against the toxicity and mutagenicity of MTX, specially at the dose 50 mg\\kg. From the results we can concluded that the AGE has a promising role in the protection of somatic cells from cytotoxic effects of methotrexate.

Assessment of the Safety of a Fermented Multi-fruit Beverage

Fruits have been widely considered as the “default health foods” as they contain numerous vitamins and minerals needed to sustain human health. To fully enhance their nutritive and flavor features while prolonging their shelf lives, fermentation strategies have been utilized to prepare healthy yet readily consumable fruit products. However, albeit their innumerable health-promoting effects, a lot of people are still concerned if consuming live bacteria and their metabolites are safe for humans. In this study, the safety of a fermented multi-fruit beverage using five different fruits (kiwis, guavas, papayas, pineapples, and grapes) was investigated. Safety assessment experiments performed on the multi-fruit beverage showed that it is nonmutagenic to five strains of Salmonella typhimurium, non-cytotoxic, and is unable to induce chromosome aberrations in Chinese Hamster Ovary K1 (CHO-K1) cells, as well as non-toxic in male ICR mice compared to the water-fed control group after 28 d of feeding. Therefore, these results collectively indicated that the fermented multi-fruit beverage is safe for human consumption.

Application of cytogenetic model Allium cepa for screening potential cytogenotoxicity of herbal-based hair dyes

Plant models may be useful as test organisms for initial screening of potential toxicity of personal care products. The objective of the present study was to assess the efficacy of the Allium cepa (common onion) test system as a bioanalytical tool for screening potential cytotoxicity and genotoxicity of herbal-based hair dye formulations. Exposure of black hair dye formulations for 48 hours resulted in root growth retardation and mitosis suppression in the root meristems of A. cepa bulbs indicating concentration dependent cytotoxicity. At the 72 hour post exposure, cytotoxic effects on the roots were reduced but not recovered completely signifying prolong toxic action of the hair dyes. The condensed nuclei was the most frequent nuclear abnormality found in the dye exposed root meristematic cells indicating the cell death process. Induction of micronuclei and chromosomal aberrations in the root meristematic cells even at the post exposure stage indicates persistent genotoxicity of the hair dyes which may be attributed to the interactive effects of chemical mixtures present in the commercial hair dye formulations. The results revealed that A. cepa test system is an effective bioanalytical tool for screening cytogenotoxicity of commercial hair dye formulations.

Evaluation of cytogenetic effects induced with ciprofloxacin and metronidazole as antibacterial agents on mouse bone marrow cells in vivo

Two of antibacterial agents were selected to evaluate the possibility of induction of chromosomal aberrations in mice bone marrow cells in vivo. The two agents, ciprofloxacin considered as antibacterial while as antibacterial and antiparasitic agent. Our data revealed that both two agents ciprofloxacin (7 mg/kg b.w.) and 30 mg/ kg b.w. induced a highly significant effect of chromosomal aberrations. We can concluded that both antimicrobial agents metronidazole and Ciprofloxacin have a marked mutagenic effects, and caution should be used in prescribing the drugs, especially in multiple courses or over long periods. The patients with severe liver disease may accumulate the drug.

Bisphenol A induces DNA damage in cells exerting immune surveillance functions at peripheral and central level

Bisphenol A (BPA) is a synthetic xenoestrogen diffused worldwide. Humans are chronically exposed to low doses of BPA from food and drinks, thus BPA accumulates in tissues posing human health risk. In this study, we investigated the effects of BPA on peripheral blood mononuclear cells (PBMC) from human healthy donors, and in glia and microglia of rat offspring at postnatal day 17 (17PND) from pregnant females who received BPA soon after coupling and during lactation and weaning. Results indicated that BPA affected Phytoemagglutinin (PHA) stimulated PBMC proliferation causing an S-phase cell cycle accumulation at nanomolar concentrations while BPA was almost ineffective in resting PBMC. Furthermore, BPA induced chromosome aberrations and the appearance of shattered cells characterized by high number of fragmented and pulverized chromosomes, suggesting that the compound could cause a massive genomic rearrangement by inducing catastrophic events. The BPA-induced DNA damage was observed mainly in TCD4+ and TCD8+ subsets of T lymphocytes and was mediated by the increase of ERK1/2 phosphorylation, p21/Waf1 and PARP1 protein expression. Intriguingly, we observed for the first time that BPA-induced effects were associated to a sex specific modulation of ERα and ERβ in human PBMC. Immunofluorescence analysis of rat hippocampus corroborated in vitro findings showing that BPA induced ɣH2AX phosphorylation in microglia and astrocytosis by decreasing ERα expression within the dentate gyrus. Overall these results suggest that BPA can alter immune surveillance functions at both peripheral and central level with a potential risk for cancer, neuroinflammation and neurodegeneration.

ВИЯВЛЕННЯ МОЖЛИВОЇ ГЕНОТОКСИЧНОЇ НЕБЕЗПЕКИ ЗА ВИКОРИСТАННЯ СИНТЕТИЧНОГО ХАРЧОВОГО АРОМАТИЗАТОРА «ВИШНЯ»

Components of flavourings are usually presented by xenobiotics – improper to the living organisms chemical compounds, that not get into the people`s organism with natural products. Every xenobiotic, getting into the organism, can be included in metabolism, influence the genetic material of the cell and therefore lead to more or less important consequences. This work is dedicated to detection of possible mutagenic activity of synthetic flauvoring «CHERRY AS00640» with using pro- and eukaryotic test-systems. Induction of chromosome aberration had been studied in two test-systems Allium cepa and Mus musculus using recommended by producer day dose and also doses that was tenfold increased or reduced. In the test on the meristem cells of onion roots at the different concentrations the chromosome aberrations level under the flavouring action had been exceeded control value. Among the anomalies the most often were double fragment that are the result of deletions and the single and double dicentrics formation as a result of translocation processes. On the mouse bone marrow cells preparations were detected aneuploidy cells and also modificated sets of chromosomes. Results of this test correlate with the results received by us in ana-thelophase test on A. cepa , in all cases were observed dose depended effect. Tests for induction of dominant-lethal mutations in Drosophila melanogaster have showed that chemical components of «CHERRY AS00640» flavouring may lead to the emergence of varied changes in genes and chromosomes, which are responsible for normal passing the spermatogenesis processes. Whereas the flavouring components usually are presented by xenobiotics that in higher eukaryotes organisms may be total or partial biotransformed that are presented by whole complex both enzymatic and spontaneous transformations. It had been conducted researches by us using the Ames test both with and without metabolic activation on Salmonella typhimurium. On the Ames test without the metabolic activation was detected induction of gene mutation in comparison with the control under the all studied dose only by the frameshift mechanism. According to the research results with the adding microsomal fraction of homogenate of the rat`s liver mutagenic activity with the using of TA-98 strain was not detected which evidence of possibility of formation less active metabolites in the transformation processes in comparison with source ingredients of flavouring which thus leads to decrease the risk of genotoxic effects of native product.

Preclinical safety assessment of pathogen reduced red blood cells treated with amustaline and glutathione.

ABSTRACTBACKGROUNDThe nucleic acid targeted pathogen reduction (PR) system utilizing amustaline (S‐303) and glutathione (GSH) is designed to inactivate blood‐borne pathogens and leukocytes in red blood cell concentrates (PR‐RBCC). Inactivation is attained after amustaline intercalates and forms covalent nucleic acid adducts preventing replication, transcription, and translation. After pathogen inactivation, amustaline spontaneously hydrolyzes to S‐300, the primary negatively charged reaction product; amustaline is below quantifiable levels in PR‐RBCC. GSH quenches free unreacted amustaline.STUDY DESIGN AND METHODSThe genotoxic and carcinogenic potential of PR‐RBCC, the reaction by‐products, and S‐300 were assessed in accordance with the International Conference on Harmonization (ICH) guidelines and performed in compliance with the Food and Drug Administration (FDA) good laboratory practice standards, 21 CFR Part 58. in vitro bacterial reverse mutagenicity and chromosomal aberration assays were performed with and without exogenous S9 metabolic activation, and in in vivo clastogenicity and carcinogenic assays using validated murine models.RESULTSPR‐RBCCs were not genotoxic in vitro and in vivo and were non‐carcinogenic in p53+/− transgenic mice transfused over 26 weeks. Estimated safety margins for human exposure ranged from >90 to >36 fold for 2 to 5 PR‐RBCCs per day, respectively. PR‐RBCCs and S‐300 did not induce chromosome aberration in the in vivo murine bone marrow micronucleus assay at systemically toxic doses.CONCLUSIONSPR‐RBCCs did not demonstrate genotoxicity in vitro or in vivo and were not carcinogenic in vivo. These studies support the safety of PR‐RBCCs and suggest that there is no measurable genotoxic hazard associated with transfusion of PR‐RBCCs.

Cytotoxic Assessment of Liquors: Whisky and Country Wine

Treatment of different concentrations of whisky and country wine for different time periods showed positive cytotoxic effects on Allium cepa root meristem. Effects included inhibition of mitotic index and induction of chromosomal aberrations like clumping, stickiness, early separation, laggard, bridge, fragment, deform chromosome, exclusion, disturbed polarity, bi- and -multinucleated cells, micronuclei, nuclear budding etc. Such cytotoxic effects warrant consumption of wine for health benefits.

Potential agricultural use of a sub-product (olive cake) from olive oil industries composting with soil

J Pharm Pharmacogn Res 8(1): 43-52, 2020. Original Article Potential agricultural use of a sub-product (olive cake) from olive oil industries composting with soil [Uso agrícola potencial de un subproducto (alperujo) de las industrias del aceite de oliva compostado con suelo] Ariadna Hammann1, Lorena M. Ybañez1, María I. Isla2, Mirna Hilal1,2* 1Centro de Estudios de Especies Vegetales de Interés Regional (CEVIR). Facultad de Ciencias Exactas y Naturales – Universidad Nacional de Catamarca. Belgrano 300, Catamarca capital, Catamarca, Argentina. 2Instituto de Bioprospección y Fisiología Vegetal (INBIOFIV, UNT-CONICET). Facultad de Ciencias Naturales e IML. San Lorenzo 1469, S. M. de Tucumán, Tucumán, Argentina. *E-mail: mhilal@csnat.unt.edu.ar Abstract Context: Olive cake and olive mill wastewater are by-products of olive oil industries. Olive cake is not currently being exploited. Aims: To evaluate the cytotoxicity and genotoxicity induced in Allium cepa root meristems by olive cake in various preparations (aqueous dilutions of olive cake and mixtures of olive cake with soil before and after a composting process). Methods: Olive cake aqueous dilutions as well as fresh and composted olive cake – soil mixtures were obtained. Samples were assayed on Allium cepa L roots and the phenolic content was also determined. Results: Aqueous dilutions showed acute genotoxicity with a mitotic index dramatic reduction and a high number of cell abnormalities. Olive cake induced chromosome aberrations such as bridges, stickiness, and laggard chromosomes and cell aberrations such as strap, folded, giant and binucleated cells. Anomalies increase with polyphenol concentration, both in aqueous dilutions and in mixtures of olive cake – soil without composting. Composted mixtures did not exhibit cell toxicity up to 10% of olive cake although they can decrease the mitotic index, which would produce a reduction in plant growth. Conclusions: Results indicate the varied behavior of olive cake according to sample preparation and suggest the possible use of this by-product incorporated to soils and subjected to composting.

Is in vivo and ex vivo irradiation equally reliable for individual Radiosensitivity testing by three colour fluorescence in situ hybridization?

BackgroundIndividual radiosensitivity is influencing the outcome of radiation therapy. A general ex vivo testing is very work-intensive. It is of interest to see if a significant prediction concerning the sensitivity can be made by in vivo irradiation during radiation treatment.MethodsBlood samples of 274 patients with rectal cancer and 43 lung cancer patients receiving radiotherapy were examined after 2 Gy ex vivo and in vivo ionizing radiation. Chromosomes # 1, 2 and 4 were stained by the 3-color-fluorescence in situ hybridization. Chromosomal aberrations were analyzed as breaks per metaphase (B/M). The deposited energy per session was calculated for each patient.ResultsWeak correlation could be found between the chromosomal aberrations ex and in vivo. Though receiving significantly smaller deposited energy during radiation therapy (RT) the lung cancer cohort displayed B/M values similar to the rectal cancer cohort. Considering the individual deposit energy differences improved slightly the correlation.ConclusionsAs various factors influence the induction of chromosomal aberrations it seems not feasible to estimate individual radiosensitivity via in vivo irradiation. An ex vivo estimation of individual radiosensitivity should be preferred.

Genetic, epigenetic, and lineage-directed mechanisms in benzene-induced malignancies and hematotoxicity targeting hematopoietic stem cells niche.

Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to benzene has been linked to the incidences of hematological disorders and malignancies. Previous studies have shown that benzene may act via multiple modes of action targeting HSCs niche, which include induction of chromosomal and micro RNA aberrations, leading to genetic and epigenetic modification of stem cells and probable carcinogenesis. However, understanding the mechanism linking benzene to the HSCs niche dysregulation is challenging due to complexity of its microenvironment. The niche is known to comprise of cell populations accounted for HSCs and their committed progenitors of lymphoid, erythroid, and myeloid lineages. Thus, it is fundamental to address novel approaches via lineage-directed strategy to elucidate precise mechanism involved in benzene-induced toxicity targeting HSCs and progenitors of different lineages. Here, we review the key genetic and epigenetic factors that mediate hematotoxicological effects by benzene and its metabolites in targeting HSCs niche. Overall, the use of combined genetic, epigenetic, and lineage-directed strategies targeting the HSCs niche is fundamental to uncover the key mechanisms in benzene-induced hematological disorders and malignancies.

The ability of Mycophenolate Mofetil to induce chromosome aberration and DNA damage in Mus Musculus Mice

Mycophenolate mofetil (MMF, cellcept) is widely used in maintenance immunosuppressive therapy for prevention refractory rejection in sold organ transplant recipients. MMF is orally used, and rapidly metabolized to its active constituent Mycophenolic acid. MPA is an inhibitor of Inosine Monophosphate Dehydrogenase ΙΙ (IMPDH ΙΙ) in lymphocyte causing in reduction in intracellular guanine nucleotide pools and leads to inhibition of lymphocyte proliferation. MMF is considered to be an effective and safe immunosuppressive agent compared with other medicins. MMF lacks the nephrotoxicity. But it has important side effects, gastrointestinal and heamatological adverse effects are the most common. The results of this study show the high significant in total chromosome aberrations in treatment groups compared with control. Also there is high significant differences in total damage DNA in treatment groups than control. In conclusion, MMF may has a high genotoxicity by induced chromosome aberration and DNA damage.

Dissection and cytological mapping of chromosome arm 4VS by the development of wheat-Haynaldia villosa structural aberration library.

A cytological map of Haynaldia villosa chromosome arm 4VS was constructed to facilitate the identification and utilization of beneficial genes on 4VS. Induction of wheat-alien chromosomal structure aberrations not only provides new germplasm for wheat improvement, but also allows assignment of favorable genes to define physical regions. Especially, the translocation or introgression lines carrying alien chromosomal fragments with different sizes are useful for breeding and alien gene mapping. Chromosome arm 4VS of Haynaldia villosa (L.) Schur (syn. Dasypyrum villosum (L.) P. Candargy) confers resistances to eyespot and wheat yellow mosaic virus (WYMV). In this research, we used both irradiation and the pairing homoeologous gene (Ph) mutant to induce chromosomal aberrations or translocations. By using the two approaches, a structural aberration library of chromosome arm 4VS was constructed. In this library, there are 57 homozygous structural aberrations, in which, 39 were induced by the Triticum aestivum cv. Chinese Spring (CS) ph1b mutant (CS ph1b) and 18 were induced by irradiation. The aberrations included four types, i.e., terminal translocation, interstitial translocation, deletion and complex structural aberration. The 4VS cytological map was constructed by amplification in the developed homozygous aberrations using 199 4VS-specific markers, which could be allocated into 39 bins on 4VS. These bins were further assigned to their corresponding physical regions of chromosome arm 4DS based on BLASTn search of the marker sequences against the reference sequence of Aegilops tauschii Cosson. The developed genetic stocks and cytological map provide genetic stocks for wheat breeding as well as alien gene tagging.

Genotoxic properties of Betonica officinalis, Gratiola officinalis, Vincetoxicum luteum and Vincetoxicum hirundinaria extracts

Genotoxicity of B. officinalis, G. officinalis, V. luteum and V. hirundinaria extracts, which demonstrated strong antioxidant capacity, was tested using chromosome aberration, sister chromatid exchange (SCE), cytokinesis-block micronucleus and alkaline single-cell gel electrophoresis (comet) assays in human lymphocytes in vitro and Ames Salmonella/microsome test. All tested extracts were not mutagenic in S. typhimurium strains TA98 and TA100 with and without metabolic activation and did not induce chromosome aberrations in human lymphocytes in vitro. Extract from G. officinalis was the only one, which induced significant increase in micronuclei, indicating possible aneugenic effect. All investigated plant extracts induced DNA damage evaluated by the comet assay, while B. officinalis and V. luteum extracts induced slight increase in SCE values. The determined variation in response might be due to the plant extract tested and donor susceptibility.

Nitric Oxide Is Involved in Heavy Ion-Induced Non-Targeted Effects in Human Fibroblasts.

Previously, we investigated the dose response for chromosomal aberration (CA) for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) particles, and showed that the dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Our results suggested that the simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. Nitric oxide (NO) has been reported as a candidate for intercellular signaling for NTE in many studies. In order to estimate the contribution of NTE components in induced CA, we measured CA with and without an NO scavenger in normal skin fibroblasts cells after exposure to 600 MeV/u and 1 GeV/u 56Fe ions, less than one direct particle traversal per cell nucleus. Yields of CA were significantly lower in fibroblasts exposed to the NO scavenger compared to controls, suggesting involvement of NO in cell signaling for induction of CA. Media transferred from irradiated cells induced CA in non-irradiated cells, and this effect was abrogated with NO scavengers. Our results strongly support the importance of NTE contributions in the formation of CA at low-particle fluence in fibroblasts.

Chromosome instability caused by mutations in the genes involved in transcription and splicing

ABSTRACTMutations in molecules involved in transcription and splicing can cause chromosome instability such as sister chromatid exchanges. We isolated and characterized responsible genes from mammalian temperature-sensitive mutant cells showing chromosome instability. A mutation in the largest subunit of RNA polymerase II affected DNA synthesis in S phase-arrested cells, resulting in abnormal induction of sister chromatid exchanges. The yeast mutant harboring a homologous mutation showed very similar phenotype to that of the mammalian mutant. A mutation in Smu1, which is involved in splicing, also affected DNA synthesis in S and G2 phase-arrested cells, resulting in abnormal induction of sister chromatid exchanges and chromosomal aberrations. These cells showed a connection between defects of RNA metabolism and induction of chromosome instability. Genome instability appeared to be caused by links between RNA metabolism and replication resulting in genomic recombination. RNA metabolism can be regarded as one possible driver of genome modification triggering genome evolution

Alleviation of cadmium-induced genotoxicity and cytotoxicity by calcium chloride in faba bean (Vicia faba L. var. minor) roots.

Alleviation of cadmium-induced root genotoxicity and cytotoxicity by calcium chloride (CaCl2) in faba bean (Vicia faba L. var. minor) seedlings were studied. Faba bean seeds were treated with H2O or 2% CaCl2 for 6h before germination. Seeds were then exposed to 0 and 50µM CdCl2 concentrations for 7days. Genotoxic damaging effects of Cd was examined through the determination of the mitotic index (MI), chromosomal aberrations (CA) and micronucleus (MN) in the meristem cells of faba bean roots. Similarly, effects of Cd stress on metal accumulation, total membrane lipid contents, total fatty acid composition (TFA), lipid peroxidation as indicated by malondialdehyde production, soluble protein and non-protein thiols (NP-SH) contents, hydrogen peroxide production and the activities of superoxide dismutase (SOD), catalase (CAT) and guaiacol peroxidase (GPX) were evaluated after 7days of Cd stress in the seedling roots. Cd stress resulted in the reduction of MI, in addition toMN formation and CA induction in the roots of non-primed seeds (treated with H2O). Moreover, Cd induced lipid peroxidation, H2O2 overproduction and loss of membrane lipid amount and soluble protein content, and changes in the TFA composition in roots of faba bean seedlings. SOD activity declined, but CAT and GPX activities increased. However, seed pre-treatment with CaCl2 attenuated the genotoxic and cytotoxic effects of Cd on Vicia faba roots. The results showed that CaCl2 induced reduction of Cd accumulation, improved cell membrane stability and increased the antioxidant defence systems, thus reducing and alleviating Cd genotoxicity and oxidative damage.

Evaluation of in vitro and in vivo genotoxic and antigenotoxic effects of Rhus coriaria

Rhus coriaria has been important in the treatment of many diseases in traditional use. In this content, the genotoxic, antigenotoxic, and oxidative stress effects of methanol extract of R. coriaria (RCE) were investigated in this study. Two hundred fifty, 500, or 750 µg/mL concentrations of RCE were not found to have DNA damaging effect on pET22-b(+) plasmid and were unable to induce micronuclei in human lymphocytes (24 or 48 h treatment period). However, it did not inhibit the genotoxic effect of mitomycin-c (0.25 µg/mL). Cytotoxic effects of RCE were investigated using mitotic index (MI) and nuclear division index (NDI). Five hundred, 1000, and 2000 mg/kg concentrations of RCE did not induce chromosome aberrations in rat bone marrow cells for 12 or 24 h treatment period. In addition, 2000 mg/kg concentration of RCE showed an antigenotoxic effect by decreasing to genotoxic effect of 400 mg/kg urethane at 12 and 24 h treatment periods. RCE showed cytotoxic effects by significantly decreasing NDI. Moreover, RCE increased cytotoxic effect of Mitomycin C (MMC). However, RCE did not induce cytotoxicity in rat bone marrow cells. The highest concentration of RCE reduced total oxidant level in 12 h treatment. Interestingly, the lowest total oxidant level was found in rats blood treated with the lowest concentration RCE and urethane together. Thousand and 2000 mg/kg concentrations of RCE decreased total antioxidant levels of rat blood at 24 h treatment period. Our results showed that RCE possess cytotoxic effect in short-term treatments in vitro. However, it does not demonstrate genotoxic or cytotoxic effects in vivo.