Estimating genotoxic effects of anticancer drugs using cytokinesis-block micronucleus assay on human lymphocytes

Here we review the current experience of using cytokinesis-block micronucleus (CBMN) assay on cultures of human lymphocytes to evaluate genotoxic effects of anticancer drugs. Having performed search in PubMed, Scopus, Web of Science, TOXLINE, and the Cochrane Library, we identified a total of 172 relevant studies. Out of them, 89 were conducted in vitro, and 41 were published within the last decade. The mentioned studies concordantly demonstrated a significant increase in micronuclei, protrusions, nucleoplasmic bridges, and a decrease in proliferation in cells treated with anticancer drugs in a time- and dose-dependent manner. Notably, the results of CBMN assay are consistent with the data obtained from other cytogenetic techniques (comet assay, chromosomal aberration analysis, analysis of mutations in housekeeping genes, and fluorescence in situ hybridisation). Conclusion. CBMN assay permits a reliable evaluation of the mutagenic effects related to anticancer drugs.

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Genotoxic Effects Induced by Fotemustine and Vinorelbine in Human Lymphocytes

Zeitschrift für Naturforschung C ◽

10.1515/znc-2006-11-1220 ◽

2006 ◽

Vol 61 (11-12) ◽

pp. 903-910 ◽

Cited By ~ 8

Author(s):

Serap Çelikler ◽

Rahmi Bilaloğlu ◽

Nilüfer Aydemir

Keyword(s):

Mitotic Index ◽

Human Lymphocytes ◽

Vinca Alkaloid ◽

Test Group ◽

Sister Chromatid Exchanges ◽

Specific Response ◽

Dependent Manner ◽

Genotoxic Effects ◽

Dose Dependent

Abstract The aim of this study was to investigate the in vitro genotoxic effects of the anticancer drugs fotemustine and vinorelbine on human lymphocytes and to determine individual and sex-related responses to these drugs. Fotemustine is a DNA-alkylating drug while vinorelbine is a semi-synthetic Vinca alkaloid. The study was carried out with twenty independent healthy donors for each drug. We have tested the ability of these drugs to induce chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) as well as effect on the mitotic index (MI) in cultured human lymphocytes. Fotemustine was shown to induce CAs and SCEs at all concentrations tested (2, 4 and 8 μg/ml) in a dose-dependent manner. Additionally it also decreased the mitotic index in a similar dose-dependent manner. Vinorelbine had no effect on structural CAs, but it significantly increased the numerical CAs at all doses tested (0.5, 1 and 2 μg/ml). Vinorelbine also induced SCE events and increased the MI values. Two-way analyses of variance were used to compare the individual and gender-related susceptibilities to fotemustine and vinorelbine with respect to the CA, SCE and MI values. The results indicated that individuals in fotemustine treatment groups showed different genotoxic responses with respect to CA and SCE induction and additional findings indicated a gender-specific response in this group. Individuals in the vinorelbine test group also exhibited statistically significant numerical CA, SCE and MI responses to vinorelbine. A statistically significant gender-related SCE response to this drug was also evident. This study indicates that these drugs have potentially harmful effects on human health.

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A Cytogenetic Approach to the Study of Genotoxic Effects of Fungicides: An in Vitro Study in Lymphocyte Cultures with Thiophanate-methyl

Alternatives to Laboratory Animals ◽

10.1177/026119299602400421 ◽

1996 ◽

Vol 24 (4) ◽

pp. 597-601

Author(s):

Patrizia Hrelia ◽

Carmela Fimognari ◽

Fernanda Vigagni ◽

Francesca Maffei ◽

Giorgio Cantelli-Forti

Keyword(s):

Human Peripheral Blood ◽

Human Lymphocytes ◽

In Situ Hybridisation ◽

In Vitro Study ◽

Peripheral Blood Lymphocytes ◽

Fluorescence In Situ Hybridisation ◽

Thiophanate Methyl ◽

Mechanisms Of Toxicity ◽

Genetic Level

This study was designed to evaluate the mechanisms of genetic damage by fungicides in cultured human peripheral blood lymphocytes by means of a molecular cytogenetic approach. For example, thiophanate-methyl (30μg/ml-300μg/ml) was shown to significantly induce chromosome aberrations and micronuclei in human lymphocytes cultured in vitro. Fluorescence in situ hybridisation with centromeric DNA probes demonstrated that most micronuclei induced by thiophanate-methyl did not show any centromeric signals, indicating a relatively stronger clastogenic activity. Results obtained with thiophanate-methyl showed that a comprehensive examination of the mechanisms of toxicity at the genetic level provides valuable information, which is of importance in the safety assessment of the fungicide.

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The Effects of Taurine on Permethrininduced Cytogenetic and Oxidative Damage in Cultured Human Lymphocytes

Archives of Industrial Hygiene and Toxicology ◽

10.2478/10004-1254-63-2012-2114 ◽

2012 ◽

Vol 63 (1) ◽

pp. 27-34 ◽

Cited By ~ 9

Author(s):

Hasan Turkez ◽

Elanur Aydin

Keyword(s):

Oxidative Damage ◽

Textile Industry ◽

Human Lymphocytes ◽

Sister Chromatid Exchanges ◽

Dependent Manner ◽

Beneficial Effects ◽

Oxidative Damages ◽

Total Oxidative Stress ◽

Oxidative Effects

The Effects of Taurine on Permethrininduced Cytogenetic and Oxidative Damage in Cultured Human LymphocytesPermethrin (PM) is a common pyrethroid pesticide used to control pests in agriculture, forestry, horticulture, health care, homes, and textile industry. It is confirmed as a strong mutagen in animals and humans. Taurine (TA) is an amino acid found in mammalian tissues that protects the cell against DNA damage. In this study, we investigated whether supplementation of human lymphocyte cultures with TA (in the concentrations of 25 μg mL-1, 50 μg mL-1and 100 μg mL-1) provided any protection against PM toxicity applied in the concentration of 200 μg mL-1. Genotoxicity was assessed using the micronucleus (MN) and sister chromatid exchanges (SCE) tests. In addition, we measured the total antioxidant capacity (TAC) and total oxidative stress (TOS) levels in the plasma to determine oxidative effects. PM increased SCE and MN levels and altered TAC and TOS levels. TA alone did not affect SCE and MN levels compared to controls, regardless of the concentration applied. In addition, it increased TAC levels without changing TOS levels. Moreover, it significantly buffered the negative cytogenetic and oxidative effects induced by PM in a clear dose-dependent manner. In conclusion, this study is the first to evidence the beneficial effects of TA against PM-induced DNA and oxidative damagesin vitro.

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Micronucleus assay in human lymphocytes after exposure to alloxydim sodium herbicide in vitro

Cytotechnology ◽

10.1007/s10616-014-9746-8 ◽

2014 ◽

Vol 67 (6) ◽

pp. 1059-1066 ◽

Cited By ~ 2

Author(s):

Dilek Akyıl ◽

Arzu Özkara ◽

S. Feyza Erdoğmuş ◽

Yasin Eren ◽

Muhsin Konuk ◽

...

Keyword(s):

Human Lymphocytes ◽

Micronucleus Assay

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Genotoxic Effects of Amplitude-Modulated Microwaves on Human Lymphocytes Exposed in Vitro under Controlled Conditions

Electro- and Magnetobiology ◽

10.3109/15368379509030726 ◽

1995 ◽

Vol 14 (3) ◽

pp. 157-164 ◽

Cited By ~ 24

Author(s):

G. D'ambrosio ◽

M. B. Lioi ◽

R. Massa ◽

M. R. Scarfi ◽

O. Zeni

Keyword(s):

Human Lymphocytes ◽

Genotoxic Effects ◽

Controlled Conditions

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Cytotoxic and genotoxic effects of calcium silicates on human lymphocytes in vitro

Mutation Research/Genetic Toxicology ◽

10.1016/0165-1218(93)90033-a ◽

1993 ◽

Vol 319 (1) ◽

pp. 81

Keyword(s):

Human Lymphocytes ◽

Genotoxic Effects ◽

Calcium Silicates

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CircSERPINE2 protects against osteoarthritis by targeting miR-1271 and ETS-related gene

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214786 ◽

2019 ◽

Vol 78 (6) ◽

pp. 826-836 ◽

Cited By ~ 26

Author(s):

Shuying Shen ◽

Yizheng Wu ◽

Junxin Chen ◽

Ziang Xie ◽

Kangmao Huang ◽

...

Keyword(s):

In Situ Hybridisation ◽

Rabbit Model ◽

Pathological Process ◽

Luciferase Reporter ◽

Circular Rnas ◽

Fluorescence In Situ Hybridisation ◽

Related Gene ◽

Downstream Target

ObjectivesCircular RNAs (circRNA) expression aberration has been identified in various human diseases. In this study, we investigated whether circRNAs could act as competing endogenous RNAs to regulate the pathological process of osteoarthritis (OA).MethodsCircRNA deep sequencing was performed to the expression of circRNAs between OA and control cartilage tissues. The regulatory and functional role of CircSERPINE2 upregulation was examined in OA and was validated in vitro and in vivo, downstream target of CircSERPINE2 was explored. RNA pull down, a luciferase reporter assay, biotin-coupled microRNA capture and fluorescence in situ hybridisation were used to evaluate the interaction between CircSERPINE2 and miR-1271-5 p, as well as the target mRNA, E26 transformation-specific-related gene (ERG). The role and mechanism of CircSERPINE2 in OA was also explored in rabbit models.ResultsThe decreased expression of CircSERPINE2 in the OA cartilage tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of extracellular matrix (ECM). Mechanistically, CircSERPINE2 acted as a sponge of miR-1271-5 p and functioned in human chondrocytes (HCs) through targeting miR-1271-5 p and ERG. Intra-articular injection of adeno-associated virus-CircSERPINE2-wt alleviated OA in the rabbit model.ConclusionsOur results reveal an important role for a novel circRNA-CircSERPINE2 in OA progression. CircSERPINE2 overexpression could alleviate HCs apoptosis and promote anabolism of ECM through miR-1271-ERG pathway. It provides a potentially effective therapeutic strategy for OA progression.

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