Discrimination between genotoxicity and cytotoxicity in the induction of DNA double-strand breaks in cells treated with etoposide, melphalan, cisplatin, potassium cyanide, Triton X-100, and γ-irradiation

Vock, Esther; Lutz, Werner; Hormes, P; Hoffmann, Heike; Vamvakasa, S

doi:10.1016/s1383-5718(98)00019-9

Cited by 78 publications

(34 citation statements)

References 32 publications

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“…Surrallés et al [1995] reported that the cytotoxicity of some pyrethroid insecticides in vitro may be related to the presence of methyl groups in the cyclopropane ring. On the other hand, it was reported that the substances caused cytotoxicity by inducing the CAs and DNA double-strand breaks [Armstrong et al, 1992;Galloway et al, 1998;Hillard et al, 1998;Vock et al, 1998;Kirkland and Müller, 2000]. In this study, a-cypermethrin most probably had a cytotoxic effect by inducing the structural CA.…”

Section: Discussionmentioning

confidence: 59%

The in vitro genotoxic effects of a commercial formulation of α‐cypermethrin in human peripheral blood lymphocytes

Kocaman

Topaktaş

2008

Environ and Mol Mutagen

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a-Cypermethrin, a highly active pyrethroid insecticide, is effective against a wide range of insects encountered in agriculture and animal husbandry. The potential genotoxicity of a commercial formulation of a-cypermethrin (Fastac 100 EC, containing 10% a-cypermethrin as the active ingredient) on human peripheral lymphocytes was examined in vitro by sister chromatid exchange (SCE), chromosomal aberrations (CAs), and micronucleus (MN) tests. The human lymphocytes were treated with 5, 10, 15, and 20 lg/ml of a-cypermethrin for 24-and 48-hr. a-Cypermethrin induced SCEs and CAs significantly at all concentrations and treatment times and MN formation was significantly induced at 5 and 10 lg/ml of a-cypermethrin when compared with both the control and solvent control. Binuclear cells could not be detected sufficiently in the highest two concentration of a-cypermethrin (15 and 20 lg/ml) for both the 24-and 48-hr treatment times. a-Cypermethrin decreased the proliferation index (PI) at three high concentrations (10, 15, and 20 lg/ml) for both treatment periods as compared with the control groups. In addition, acypermethrin reduced both the mitotic index (MI) and nuclear division index (NDI) significantly at all concentrations for two treatment periods. The PI and MI were reduced by a-cypermethrin in a concentration-dependent manner during both treatment times. In general, a-cypermethrin showed higher cytotoxic and cytostatic effects than positive control (MMC) at the two highest concentrations for the 24-and 48-hr treatment periods. The present study is the first to report the genotoxic and cytotoxic effects of commercial formulation of a-cypermethrin in peripheral blood lymphocytes. Environ. Mol. Mutagen. 50:27-36, 2009. V V C 2008 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 59%

The in vitro genotoxic effects of a commercial formulation of α‐cypermethrin in human peripheral blood lymphocytes

Kocaman

Topaktaş

2008

Environ and Mol Mutagen

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“…In A549 cells, etoposide has been reported to induce double-strand DNA breaks after 8 h while the cells remained viable [9]. Etoposide was shown to rapidly and profoundly upregulate p53, an inducer of apoptosis [20,21], in the later phases of apoptosis but immediately before caspase-3 activation [21].…”

Section: Discussionmentioning

confidence: 98%

“…It is highly toxic to actively replicating cells and so is used as a chemotherapeutic agent to treat certain types of cancers such as leukemia. Triton X-100 is a detergent and has been used as a cytotoxic agent to induce cell death through extragenomic mechanisms [9]. Detergents affect the cell membrane by solubilizing the lipids through the disruption of hydrophobic contact, thus destroying the lipid bilayer.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of Bacterial-Derived Toxins to Immortal Lung Epithelial and Macrophage Cells

Peterson

Collier

Katterman

et al. 2009

Appl Biochem Biotechnol

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Health risks associated with inhalation and deposition of biological materials have been a topic of great concern due to highly publicized cases of inhalation anthrax, of new regulations on the release of particulate matter, and to increased concerns on the hazards of indoor air pollution. Here, we present an evaluation of the sensitivity of two immortal cell lines (A549, human lung carcinoma epithelia) and NR8383 (rat alveolar macrophages) to a variety of bacterial-derived inhalation hazards and simulants including etoposide, gliotoxin, streptolysin O, and warfarin. The cell response is evaluated through quantification of changes in mitochondrial succinate dehydrogenase activity, release of lactate dehydrogenase, initiation of apoptosis, and through changes in morphology as determined by visible light microscopy and scanning electron microscopy. These cells display dose-response relations to each toxin, except for triton which has a step change response. The first observable responses of the epithelial cells to these compounds are changes in metabolism for one toxin (warfarin) and alterations in membrane permeability for another (gliotoxin). The other four toxins display a similar time course in response as gauged by changes in metabolism and loss of membrane integrity. Macrophages are more sensitive to most toxins; however, they display a lower level of stability. This information can be used in the design of cell-based sensors responding to these and similar hazards.

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“…Bazı araştırıcılar da kimyasal maddelerin in vitro sitotoksik etkilerinin DNA çift iplik kırıklarının oluşmasına bağlı olarak ortaya çıktığını bildirmişlerdir [36,37]. Giri ve arkadaşları [38] kromozomal anormalliklerin kimyasal maddelerde bulunan alkilleyici özellikten kaynaklandığını, alkilleyici ajanların da DNA hasarına yol açtığını belirtmişlerdir.…”

Section: Tartişma Ve Sonuçunclassified

Anabolik Steroidlerin Genotoksik ve Sitotoksik Etkilerinin İnsan Periferal Lenfosit Kültüründe Mikronükleus Test Tekniğiyle Araştırılması

Çolak

Ayar

Uysal

2016

CSJ

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Özet. Spor tarihi boyunca genç yaştaki bir çok sporcunun doping amacıyla anabolik-androjenik steroidleri yoğun olarak kullandığı bilinmektedir. Bu çalışmayla, kullanımı yasaklanmış olsa da yapılan araştırmalarda illegal olarak halen sıkça kullanılmakta olan Nandrolone Decanoate (Deca-durabolin®) ve Stanozolol (Winstrol) doping maddelerinin olası genotoksik, mutajenik ve sitotoksik etkilerinin insan kan kültüründe in vitro mikronükleus testi ile belirlenmesi amaçlanmıştır. Bu amaçla doping maddelerinin farklı konsantrasyonları (1, 10, 25, 50, 75 ve 100 mM) hazırlanmış ve kan kültürüne uygulanmıştır. Genotoksik etki için mikronükleus frekansları, sitotoksik etki için ise Nükleer Bölünme İndeksi (NBİ) hesaplanmıştır. Elde edilen veriler, çözücü olarak kullanılan dimetil sülfoksit (DMSO) ile hazırlanan negatif kontrol grubuyla ve genotoksik etkisi çok iyi bilinen Etil metansülfonat (EMS) ile hazırlanmış pozitif kontrol grubuyla karşılaştırılmıştır. Bu sonuçlara göre; çalışmamızda kullandığımız doping maddelerinden Nandrolone Decanoate özellikle son iki konsantrasyonda (75 ve 100 mM) insan periferal lenfositlerinde mikronükleus frakansını istatistiksel olarak anlamlı (p< 0,05) bir şekilde artırmıştır. Ayrıca NBİ oranlarına bakıldığında da özellikle son iki konsantrasyonda kontrol grubuna göre önemli düşüşler tespit edilmiştir. Bununla birlikte diğer doping maddesi olan Stanozolol ise sadece son konsantrasyonda (100 mM) anlamlı artışlara neden olmuşken NBİ değerini etkilememiştir. Tüm elde ettiğimiz sonuçlardan her iki doping maddesinin de yüksek konsantrasyonlarda genotoksik ve sitotoksik etkiler yaratabileceği bu nedenle kullanımlarının tehlikeli olabileceği sonucuna ulaşılmıştır.Anahtar Kelimeler: Genotoksisite, Lenfosit kültürü, Mikronükleus, Nandrolone Decanoate, Stanozolol The Investigation of the Cytotoxic and Genotoxic Effcts of the Anabolic Steroids in Human Peripheral Lymphocytes Culture by Micronucleus TestAbstract. Throughout the sports history anabolic -androgenic steroids are known to be used intensively for the purpose of doping in athletes at very young age. In this study, the genotoxic, mutagenic and cytotoxic effects of possible doping substances, Nandrolone Decanoate (Deca-durabolin®) and stanozolol (Winstrol) that are currently being illegally widely used, though the use of them are prohibited, are used to determine in human blood culture by in vitro micronucleus test. For this purpose, different concentrations of doping substances (1, 10, 25, 50, 75 and 100 mM) were prepared and applied to the blood culture. For genotoxic effects micronucleus frequency and for to the cytotoxic effects Nuclear Fission Index (NBI) was calculated. The obtained data was compared to the negative control group that were prepeared with dimethyl sulfoxide (DMSO) as solvent and a well-known genotoxic effects of Ethyl methanesulfonate (EMS) as positive control group. Based on these results; in our study the doping substances Nandrolone decanoate caused a statistically significant (p< 0,05) increase in human peripheral lymph...

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Discrimination between genotoxicity and cytotoxicity in the induction of DNA double-strand breaks in cells treated with etoposide, melphalan, cisplatin, potassium cyanide, Triton X-100, and γ-irradiation

Cited by 78 publications

References 32 publications

The in vitro genotoxic effects of a commercial formulation of α‐cypermethrin in human peripheral blood lymphocytes

The in vitro genotoxic effects of a commercial formulation of α‐cypermethrin in human peripheral blood lymphocytes

Cytotoxicity of Bacterial-Derived Toxins to Immortal Lung Epithelial and Macrophage Cells

Anabolik Steroidlerin Genotoksik ve Sitotoksik Etkilerinin İnsan Periferal Lenfosit Kültüründe Mikronükleus Test Tekniğiyle Araştırılması

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