Search

Seven cultivar varieties of Vicia sativa L. were used. Nucleotypic effects of telophase (2C) nuclear DNA amounts on seed weight, percent mitotic index, stomatal frequency/mm2, chlorophyll a and b content, root growth and shoot growth were determined. No correlation was observed between the DNA contents and the percent mitotic index, chlorophyll a and b content, or root growth of the cultivar varieties. However a significant correlation was observed between DNA content and the seed weight, stomatal frequency and shoot growth of the cultivar varieties.

ÖZET `ANTİNEOPLASTİK AJANLARDAN MUPHORAN VE NAVELBİNE'İN MUTAJENİK ETKİSİNİN İNSAN LENFOSİT KÜLTÜRLERİNDE ARAŞTIRILMASI` Bu çalışmada, değişik kanser tiplerinin kemoterapisinde kullanılan iki antineoplastik ajan olan Navelbine ( Vinorelbine ) ve Muphoran'ın ( Fotemustine ) genotoksik -etkileri araştırılmıştır. Bu amaçla insan lenfosit kültürlerinde kromozom aberasyon ve kardeş kromatid değişim ( SCE ) testleri gerçekleştirilmiştir. Çalışmada Muphoran bileşiği, toz halinde olduğundan steril distile suda çözülerek 2 u-g/ml, 4 fig/ml ve 8 ug/ml dozlarda steril koşullar altmda lenfosit kültürlerine verilmiştir. Kültürlere uygulanan rutin harvest yöntemi ile elde edilen preparatlara giemsa boyama yapılarak kromozom aberasyon frekansı değerlendirilmiştir. Muphoran'ın insan lenfosit kültürlerinde meydana getirdiği kromatid ve kromozom tipte kırıklarda doza bağlı olarak anlamlı bir artış gösterilmiştir. İlacın oluşturduğu toplam aberasyonlar değerlendirildiğinde de doza bağlı olarak anlamlı bir artış görülmektedir. Aynı zamanda Muphoran mitotik indeks oranlarında da doza bağlı olarak anlamlı bir düşüşe sebep olmuştur. SCE preparatlarına ise fluoresan plus giemsa boyama yapılarak SCE'ler değerlendirilmiştir. Muphoran'ın meydana getirdiği SCE oranlarında anlamlı bir artış olduğu gösterilmiştir. İlacm meydana getirdiği kromozom aberasyonları ve SCE'ler açısından kadın ve erkek bireyler arasında anlamlı bir faklılık olmadığı belirlenmiştir. İlaç dozlarına bağlı olarak meydana gelen kromozom hasarları ve SCE'lerde, doz-yanıt ilişkileri açısından bireysel farklılıklar olduğu belirlenmiştir. Diğer kanser ilacı olan Navelbine bileşiği ise, intravenöz solüsyon halinde olduğundan steril distile su ile seyreltilerek 0,5 jag/ml, 1 ig/ml ve 2 ug/ml dozlarda olmak üzere, steril koşullar altında lenfosit kültürlerine ilave edilmiştir. Kültürlere uygulanan rutin harvest yöntemi ile elde edilen preparatlara giemsa boyama tekniği uygulanarak, kromozom aberasyon frekansı değerlendirilmiştir. Navelbine uygulaması,11 lenfositlerde doza. bağlı olarak artış gösteren anlamlı bir aneuploidiye sebep olmuştur. Bunun yanında, ilacın mitoz durdurucu etkisinden kaynaklanan mitotik indekste artış söz konusu olmuştur. Ayrıca anlamlı olmayan kromatid ve kromozom kırıkları da meydana gelmiştir. SCE testi için ise, preparatlara fluoresan plus giemsa boyama yapılarak, SCE' ler değerlendirilmiştir. Navelbine uygulaması ile doza bağlı olarak SCE oranlarında anlamlı bir artış olduğu gösterilmiştir. İlacm etkisiyle oluşan kromozom aberasyonları ve SCE'lerde, doz-yanıt ilişkisi açısından, bireysel farklılıklar olduğu ortaya konmuştur. Sonuç olarak çalışmamızda genotoksik etkileri araştırılan Navelbine ve Muphoran bileşiklerinin insan lenfosit kültürlerinde kromozom aberasyon ve SCE testlerine pozitif sonuç verdikleri belirlenmiş ve önemli genotoksik etkilerinin olduğu ortaya konmuştur. Anahtar Kelimeler : Navelbine, Muphoran, İnsan, Lenfosit, Kromozom Aberasyonu, SCE, Genotoksik etki, Genotoksik Ajan, Mitotik İndeks, Alkilleyici ajan, Aneuploidojenik Ajan ABSTRACT `THE INVESTIGATION OF MUTAGENIC EFFECTS OF ANTINEOPLASTIC DRUG MUPHORAN AND NAVELBINE IN HUMAN LYMPHOCYTE CULTURES` The purpose of this study, it is aimed to determine the genotoxic effects of two antineoplastic agents that Navelbine ( Vinorelbine ) and Muphoran ( Fotemustine ) are used to treatment of several cancer types. In the peresent work, Muphoran was dissolved in sterile distilled water and added to lymphocyte cultures as 2 ug/ml, 4 u.g/ml and 8 ug/ml. Slides were prepared with routine harvesting method, stained with giemsa and chromosome aberration frequencies were scored for each culture. Muphoran increased the chromatid and chromosome type breaks in dose dependent manner. Total chromosome aberrations were also increased by Muphoran dose dependently. Muphoran significantly decreased the mitotic index ratio in all doses. Concurrently, we applied the SCE method as the second genotoxicity endpoints to lymphocyte cultures. With the Muphoran treatment, the frequency of SCE significantly increased. There were no significant differences among male and female donors with respect to to the frequency of chromosome aberrations and SCE induced by Muphoran. On the contrary, each donor responded differently and significantly that three different doses treated with Muphoran in all whole blood cultures. Other chemotherapeutic drug is Navelbine and it was diluted with sterile distilled water since it was in a solution form. This drug was added to lymphocyte cultures as three doses like 0,5 ug/ml, 1 ug/ml ve 2 ug/ml. In chromosome aberrations ( CA ) assay, Navelbine significantly and dose-dependently increased the aneuploidy induction. The mitotic index was also increased by Navelbine treatment in human lymphocyte cultures. Navelbine induced chromatid and chromosome type breaks but its frequencies were not statistically significant. In SCE assay, Navelbine significantly and dose dependently increased the freguency of SCE's too. Each donor differently andIV significantly responded to Navelbine doses regarding to chromosome aberrations and SCE's. Consequently, it has been suggested in this study that the two drugs Muphoran and Navelbine have induced chromosome aberrations and SCE's in human lymphocyte cultures and may have significant genotoxic effects. Key Words : Navelbine, Muphoran, Human, Lymphocyte, Chromosome Aberrations, SCE, Genotoxic Effect, Genotoxic Agent, Mitotic Index, Alkylating Agents, Aneuploidogenic Agents 126

Bu çalışmada, Vicia sativa L. 'nin 7 çeşit ve hattı kullanılmıştır. Telofaz ( 2C ) ve Profaz ( 4C ) DNA miktarlarının tohum ağırlığı, % Mitotik indeks, stoma frekansı/mm2, klorofil a ve b içeriği, kök büyümesi ve gövde büyümesi üzerine olan etkileri araştırılmıştır. Vicia sativa L. 'nin kullanılan çeşit ve hatlarında 2C ve 4C çekirdek DNA miktarlarında önemli varyasyon saptanmıştır. Kullanılan çeşit ve hatların DNA miktarı ile % Mitotik indeks, klorofil a ve b içeriği ve kök büyümesi arasında bir ilişki olmadığı, fakat DNA miktarı ile tohum ağırlığı, stoma frekansı ve gövde büyümesi arasında anlamlı bir ilişki olduğu belirlenmiştir. Kullanılan çeşit ve hatların DNA miktarlarının tohum ağırlığı ile kuvvetli ilişkiye sahip olduğu belirlenmiştir. % Mitotik indeks ile DNA miktarı arasında anlamlı bir ilişkinin olmadığı, stoma frekansı ile anlamlı bir ilişkinin mevcut olduğu gözlenmiştir. Klorofil a ve b içeriği ile DNA miktarları arasında herhangi bir ilişki olmadığı tespit edilmiştir. Günlere göre kök ve gövde büyüme oranları belirlenerek DNA miktarları arasındaki ilişki incelenmiştir. DNA miktarı ile kök büyümesi arasında anlamlı bir ilişki saptanamamıştır. Gövde büyümesinin erken döneminde DNA miktarı ile büyüme arasında anlamlı negatif bir ilişki ve gelişimin ilerlemesi ile birlikte anlamlı pozitif bir ilişki dikkat çekicidir. In this study, seven cultivar varieties of Vicia sativa L. have been used. Nucleotypic effects of telophase ( 2C ) and prophase ( 4C ) nuclear DNA amounts have been established upon seed weight, percent mitotic index, stomatal frequency/mm2, chlorophyll a and b content, root growth and shoot growth. A significant variation in the 2C and 4C nuclear DNA content of cultivar varieties of Vicia sativa has been established. No correlation was observed between their DNA contents and percent mitotic index, chlorophyll a and b and root growth of used of cultivar varieties. But a significant correlation was observed between DNA content and seed weight, stomatal frequency and shoot growth of cultivar varieties.

Pancreatic cancer decreases survival time and quality of life because of drug resistance and peripheral neuropathy during conventional treatment. This study was undertaken to investigate whether alpha v beta 3 integrin receptor antagonist compounds NDAT and XT199 can suppress the development of cisplatin resistance and cisplatin-induced peripheral neuropathy in an orthotopic pancreatic SUIT2-luc cancer cell mouse model. Anticancer effects of these compounds and their combination with cisplatin were assessed in this tumor mouse model with bioluminescent signaling and histopathology, and a cytokine assay was used to examine expression of inflammatory cytokines IL-1 beta, IL-6, IL-10, and TNF-alpha from plasma samples. To determine the neuroprotective effects of the compounds on cisplatin-induced peripheral neuropathy, behavioral hind-limb posture of the mice was evaluated. The combination therapy of NDAT or XT199 with cisplatin elicited greater inhibition of tumor growth and increased tumor necrosis compared to cisplatin alone. NDAT and XT199 in combination with cisplatin significantly decreased expression of pro-inflammatory cytokines IL-1 beta, IL-6, and TNF-alpha and significantly increased expression of anti-inflammatory cytokine IL-10 in comparison to cisplatin alone. Cisplatin-treated groups showed stocking-glove hind-limb posture, whereas NDAT and XT199 with cisplatin-treated groups displayed normal hind-limb posture. Results clearly suggest that NDAT and XT199 treatment with cisplatin that inactivates NF-kappa B may contribute to increased antitumor and anti-inflammatory efficacy as well as alleviate cisplatin-mediated loss of motor function in this pancreatic tumor mouse model. Pharmaceutical Research Institute at Albany College of Pharmacy Health and Sciences

Hypericum adenotrichum Spach. is an endemic plant from Turkey that is also used in folk medicine. In this study, following analyses of its chemical composition, the genotoxic/antigenotoxic effects of the methanol extract of H. adenotrichum in human lymphocyte culture were investigated using in vitro sister chromatid exchange, micronucleus and comet assays. In addition, the anti-growth effect of the extract was investigated in human breast cancer cell lines (MCF-7 and MDA-MB-231) using MTT and ATP viability assays. The mode of cell death was determined using fluorescence microscopy and biochemical methods. We found that the H. adenotrichum extract demonstrated cytotoxic and genotoxic effects in a cell type-dependent manner. At selected doses (125-500 mu g/ml), the H. adenotrichum extract exhibited significant genotoxic activity in human lymphocytes, whereas it showed anti-growth effects on cancer cell lines between 0.2 and 100 mu g/ml concentrations. The mode of cell death in cancer cells was shown to be apoptosis due to the presence of pyknotic nuclei, the cleavage of poly-(ADP-ribose) polymerase (PARP) and/or the activation of caspase-3. These results suggest that H. adenotrichum might show both cytotoxic and genotoxic effects depending on the cell type. This should be taken into account in its use for therapeutic purposes.

Transforming growth factor [31 (TGF beta 1) is a well -established inducer of the epithelial-mesenchymal transition (EMT) that is essential for the acquisition of malignant properties, such as invasion, in tumor cells. Although recent studies suggest that the EMT in tumor cells is associated with reprogramming of energy metabolism and TGF beta 1 has been shown to stimulate glycolysis in multiple primary cell lines, little is known about TGF beta l 's effect on glycolysis and glycolytic regulators in transformed cells. Given the known regulatory role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 (PFKFB3) in glycolysis and association of glycolytic activity with malignant features such as invasion, we sought to investigate whether TGF beta 1 regulates PFKFB3 expression and if PFKFB3 is involved in the TGF beta l -mediated increase in the invasive ability of the Panc1 cell cline a well -established model of TGF beta 1 -initiated EMT. Herein we demonstrate that TGF beta 1 induces PFKFB3 expression and stimulates glycolysis in Panci cells. We also show that s1RNA silencing of PFKFB3 prevents the stimulation of glycolysis and in vitro invasive ability of Panci cells by TGF beta 1. Furthermore, PFKFB3 silencing suppresses the TGFfil -mediated induction of the Snail protein, suggesting that PFKFB3 is required for the regulation of Snail expression by TGFfil. Taken together, our study identifies PFKFB3 as a key TGF beta 1 effector protein that mediates TGF beta 1's effect on Snail expression, invasion, and glycolysis.

There is an increasing demand for natural antioxidant molecules in order to replace the synthetic additives in the food industry. Gracilaria Bursa-pastoris (Gmelin) Silva was analyzed to determine its bioactive components including; the total phenolic content, total antioxidant capacity (lipid and water-soluble), vitamins (A, E and C), total protein and total carbohydrate content. In addition, the bioactive components of Gracilaria Bursa-pastoris were compared with some plants and seaweeds having antioxidant capacity. This study showed that Gracilaria bursa-pastoris contained a high total phenolic content, vitamin E, vitamin C and the antioxidant capacity. Gracilaria Bursa-pastoris can be utilized as a source of natural antioxidant molecules and could be useful for food industry.

Amifostine (WR-2721), a phosphorylated aminothiol pro-drug, is a selective cytoprotective agent in normal tissue against the toxicities associated with chemotherapy and irradiation. Fotemustine is a cancer chemotherapeutic agent that belongs to an extremely active class of alkylating compounds. Amifostine was tested for antimutagenicity against fotemustine in the somatic mutation and recombination test (SMART) in Drosophila melanogaster . Third-instar larvae that were trans -heterozygous for the two genetic markers mwh and flr were treated at different concentrations (2, 4, and 8 μg/ml for fotemustine and, 1, 2, and 4 μg/ml for amifostine) of the test compounds; for the antimutagenicity study, 8 μg/ml fotemustine plus 1 and 2 μg/ml amifostine were tested. Fotemustine showed mutagenic and recombinagenic effects in both genotypes in the wing-spot test. Amifostine significantly reduced the mutagenic and recombinagenic effects of fotemustine.

The genome is constantly exposed to agents, both exogenous and endogenous, that damage DNA. Consequently, it is very important that determination of this agents and the protective agents. In this work, we evaluated the antigenotoxic/antimutagenic activity of the crude ethanolic extracts of Codium tomentosurn Stackhouse (Chlorophyceae) (CTE), collected from The Coast of South East Marmara Sea, in human lymphocytes culture in vitro against genotoxic/mutagenic agents MMC, EMS and H2O2 by using chromosome aberration (CA), sister chromatid exchange (SCE) and micronuclei (MN) assays as experimental endpoints. Also, in the present study, we determined total phenolic content and total antioxidant capacity (in soluble lipid and water). In addition, total protein, total carbohydrate, vitamins (A. C and E) and pigments (chlorophyll a, chlorophyll b and carotene) contents were also determined. Results of CA, SCE and MN tests show that CTEs have not shown genotoxic effect. In CTE plus MMC-. EMS- or H2O2- treated cultures, CA, SCE and MN frequency which induced by MMC, EMS or H2O2 has been decreased significantly (p < 0.05-0.001). This is the first report on genotoxicity/antigenotoxicity and anti-oxidative capacity of Codium tomentosum. Our results have clearly shown that CTE has strong anti-oxidative and antigenotoxic effect. (C) 2009 Elsevier Ltd. All rights reserved.

Pyrimethamine is known to have antimalarial activities and used clinically in the therapy of toxoplasmosis and human immunodeficiency virus-associated pneumonia. In this study we aimed to test the effects of pyrimethamine on spermatogenesis in mice. For this aim, animals were given pyrimethamine as a single application and the doses were 5, 10, 20, and 40 mg/kg. For the spermatogenic effects, the sperm shape abnormality, epididymal sperm counts, and testes weights were evaluated at the end of days 7, 14, 21, 28, and 35 after single pyrimethamine injection at the first day. Pyrimethamine increased the frequency of abnormal sperm shape for all studied weeks except the first week and its germ cell stage-specific effects correspond to spermatozoa, spermatids, and spermatocytes. It also decreased the epididymal sperm counts at the end of days 28 and 35, which corresponds to the spermatocyte stage of mouse spermatogenesis.

Hypericum species are used in different folk medicines and screened for their biological activity including cancer. We, therefore, evaluated the possible cytotoxic/apoptotic and genotoxic activities of Hypericum adenotrichum Spach. and Hypericum olympicum L. Antigrowth effect was screened in human lung cancer cell lines (A549 and PC3) by the ATP viability assay, while genotoxic activity was performed using the Comet assay. Histological and biochemical methods were utilized to elucidate the cell death mode. The results indicate that the crude methanol extracts of H. olympicum L. and H. adenotrichum have both antigrowth/cytotoxic and genotoxic activities on these cells in a dose dependent manner. These extracts clearly induced apoptosis in PC3 lung cancer cell lines. In this study, we report for the first time that the H. olympicum and H. adenotrichum exhibits potential cytotoxic and genotoxic activities in lung cancer cells as well as the apoptosis-inducing roles through DNA damage in PC3 cells. Practical ApplicationsMedicinal plants are used in traditional medicine worldwide and several have been screened for their anticancer properties, we evaluated the possible cytotoxic and genotoxic activities of the Hypericum adenotrichum and Hypericum olympicum, which are still used in Turkish folk medicine. H. adenotrichum Spach., an endemic species in Turkey, and H. olympicum L., which are known as kantaron and used traditionally for their wound healing and antiseptic properties. It was found that Hypericum species showed a significant growth-inhibiting effect on human lung cancer cells and induced apoptosis-like cell death by DNA damage in PC3 lung cancer cells. These species may have a potential as anticancer agents and inspire to new improvements for medicinal chemistry.

The seed germination characteristics of three threatened Festuca sp. [F. punctoria Sm., F. cyllenica Boiss. et Heldr. subsp. uluana Markgr.-Dannenb., F. paphlagonica (St.-Yves) Markgr.-Dannenb. subsp. paphlagonica] were investigated. These species are endemic and spread on alpine belt. The study was carried out with wet-cold and dry-cold stratification throughout 15 days, different doses of GA3 (50, 100 and 150 ppm) and hormone-stratification combined treatments, and non-treatment series. We found that the germination rates of three fescue seeds for various treatment series were different. The mean germination percentage of F. cyllenica was higher (80%) than that of F. punctoria and F. paphlagonica which were fairly low (50-60%). Germination rates increased by wet-stratification treatment in F. punctoria and also increased with 100 ppm GA3 application to the seeds of F. paphlagonica. When taken into consideration the germination percentages of all fescue species, the seeds of F. punctoria and F. paphlagonica can be dormant, but the seeds of F. cyllenica are non-dormant.

Objectives: Successful cancer treatments still require more compounds to be isolated from natural sources. Thus, we have investigated anti-proliferative/apoptotic effects of methanolic extracts of lichen species Parmelia sulcata Taylor and Usnea filipendula Stirt on human lung cancer (A549, PC3), liver cancer (Hep3B) and rat glioma (C6) cells. Materials and methods: Anti-proliferative effects were monitored by MTT and adenosine triphosphate viability assays, while genotoxic activity was studied using the comet assay. Additionally, cell death mode and apoptosis assays (fluorescence staining, caspase-cleaved cytokeratin 18, caspase-3 activity and PARP cleavage) were performed. Results: Extracts produced anti-population growth effects in a dose-dependent manner (1.56–100 lg/ ml) by inducing apoptosis-like cell death. This resulted in the lines having the presence of pyknotic cell nuclei. In addition, significant increase in genetic damage in the cell lines was seen, indicating that DNA damage may have been responsible for apoptotic cell death. Conclusion: In this study, methanolic extracts of Parmelia sulcata and Usnea filipendula induced apoptosis-like cell death by causing DNA damage, to cancer cells.

The aim of this study is to determine the chemical composition, and evaluate the genotoxic, and anti-growth potency of the methanol extracts of lichen species Hypogymnia physodes (L.) Nyl. (HPE). Anti-growth effect was tested in two different human breast cancer cell lines (MCF-7 and MDA-MB-231) by the MTT and ATP viability assays and apoptosis was assayed by the caspase-cleaved cytokeratin 18 (M30-antigen). Genotoxic activity of HPE was studied using chromosome aberration and micronuclei tests in human lymphocytes culture in vitro. The chemical composition of H. physodes was analyzed by using direct thermal desorption method coupled with comprehensive gas chromatography-time of flight mass spectrometry (GCXGC-TOF/MS). Our results indicate that HPE has an anti-growth effect at relatively lower concentrations, while relatively higher concentrations are required for genotoxic activity. HPE, therefore, seems to represent a therapeutic potential and poses new challenges for medicinal chemistry.

Bu çalışmada Hypericum adenotrichum Spach. ve Hypericum olympicum L. türlerinin genotoksik/antigenotoksik etkileri insan lenfosit kültürlerinde kısa süreli in vitro genotoksisite test yöntemleri ile belirlenmeye çalışıldı. Bu amaçla in vitro, Kromozom Aberasyonu (CA),Kardeş Kromatid Değişimi (SCE), Mikronükleus (MN) ve Komet Testleri gerçekleştirildi.Sonuç olarak, çalışmada Hypericum adenotrichum ve Hypericum olympicum türlerinin insan lenfosit kültürlerinde Kromozom Aberasyonu (KA), Kardeş Kromatid Değişimi (KKD), Mikronükleus (MN) ve Komet testlerinden elde verilere göre önemli genotoksik etkilerinin olabileceği belirlendi. In this stduy, genotoxic/antigenotoxic effects of Hypericum adenotrichum Spach. and Hypericum olympicum L. species are investigated with in vitro test methods in human lymphocyte culture. For that purpose, in vitro Sister Chromatid Exchange and Micronucleus (MN) assays were performed.In conclusion, it has been suggested in this study that Hypericum adenotrichum and Hypericum olympicum extracts have induced sister chromatid exchanges, chromosome aberrration, micronucleus formation and DNA damage in human lymphocytes. So they may have significant genotoxic effects. 165

Bu çalışmada Parkinson hastalık tedavisinde kullanılan Levodopa ve Karbidopa ilaçlarının genotoksik, bir pirimidin nükleozidi olan Üridin'in antigenotoksik etkileri belirlenmeye çalışıldı. Bu amaçla in vivo fare kemik iliği Mikronükleus ve Komet Testleri gerçekleştirildi.Çalışmada Levodopa ilacı 10, 50 ve 100 mg/kg dozlarda intraperitoneal (i.p.) yolla farelere enjekte edildi. Bu ilaç ile 24 saat muamele sonunda gerçekleştirilen fare kemik iliği Mikronükleus Testinde her üç doz grubunda meydana gelen mikronükleuslu polikromatik eritrositlerin (MNPCE) oranının kontrol grubuna göre anlamlı olarak arttığı gözlendi. Komet Testi sonuçlarına göre, Levodopa uygulama gruplarında komet kuyruk uzunluğu, kuyruk % DNA, genetik hasar indeksi (GHİ) ve hasarlı hücre yüzdesinde doza bağlı olarak bir artış olduğu aynı zamanda kafa % DNA'sında istatiksel olarak bir azalmanın meydana geldiği belirlendi.Çalışmada aynı yolla uygulanan Karbidopa ilacının 1, 5 ve 10 mg/kg dozlarının genotoksik etkileri gözlenmedi.Levodopa ve Karbidopa ilaçları birlikte 10/1, 50/5 ve 100/10 mg/kg dozlarda farelere i.p. olarak uygulandı. İn vivo fare kemik iliği Mikronükleus ve Komet Testi verilerine göre 50/5 ve 100/10 mg/kg doz gruplarındaki PCE oranındaki artışın istatistiksel olarak anlamlı olduğu belirlendi (p < 0,0001). Komet Testi verilerine göre, kombine ilaç uygulamalarının Komet kuyruk uzunlukları negatif kontrol grubu ile karşılaştırıldığında 50/5 ve 100/10 mg/kg'lık doz gruplarında istatistiksel olarak anlamlı bir artış bulundu. Kuyruk % DNA oranlarında her üç doz grubunda meydana gelen artış, kafa % DNA verilerinde doz artışına bağlı olarak meydana gelen azalış ve genetik hasar indeks değerlerinde her üç doz grubunda meydana gelen artış negatif kontrolle kıyaslandığında istatistiksel olarak anlamlı olduğu belirlendi. Hasarlı hücre yüzde oranları kontrol grubu ile karşılaştırıldığında ise, 50 ve 100 mg/kg doz gruplarındaki artışın istatistiksel olarak anlamlı olduğu sonuçlarına ulaşıldı.Yapılan in vivo Mikronükleus ve Komet Testi verileri değerlendirildiğinde, kullanılan 100 mg/kg Üridin dozunun genotoksik etki göstermediği gözlendi. Üridin'in Levodopa'nın 10, 50 ve 100 mg/kg dozları ile kombine bir şekilde uygulanması sonucunda, Levodopa dozlarının meydana getirdiği MNPCE oranlarını sırasıyla 1,8, 2,15 ve 2,85 kat azalttığı belirlendi. Komet kuyruk uzunluğu oranlarını sırasıyla 2,09, 2,69 ve 4,94 kat azalttığı ve GHİ değerlerini ise, sırasıyla 2,59, 6,64 ve 6,18 kat azalttığı belirlendi.Üridin'in 100 mg/kg dozunun Levodopa/Karbidopa kombinasyonunun 10/1, 50/5 ve 100/10 mg/kg doz grupları ile birlikte uygulaması sonucunda gerçekleştirilen fare kemik iliği Mikronükleus ve Komet Testi verilerine göre, uygulanan Üridin dozunun Levodopa/Karbidopa kombine dozlarının meydana getirdiği MNPCE oranlarını sırasıyla 1,03, 2,37 ve 3,83 kat, komet kuyruk uzunluğu oranlarını sırasıyla 2,35, 3,43 ve 4,29 kat, kuyruk % DNA oranlarını sırasıyla 5,73, 15,74 ve 17,13 kat GHİ oranlarını ise, sırasıyla 3,23, 5,73 ve 5,93 kat azalttığı ve hesaplanan hasarlı hücre yüzdesi oranlarını düşürdüğü sonucuna ulaşıldı.Sonuç olarak, çalışmada genotoksik etkileri belirlenmeye çalışılan Levodopa ve Karbidopa ilaçlarının in vivo fare kemik iliği Mikronükleus ve Komet Testlerinde, Karbidopa uygulamasının genotoksik etki göstermediği sonucuna ulaşıldı. Levodopanın tek başına ve Karbidopa ile birlikte uygulanması sonucunda mikronükleus frekansının istatistiksel anlamlı bir şekilde arttığı belirlendi (p < 0,0001). Çalışmada kullanılan Üridin'in genotoksik etkisinin bulunmadığı, bunun yanı sıra Levodopa ve Levodopa/Karbidopa kombinasyonu ile birlikte kullanıldığında Levodopa ve Levodopa/Karbidopa kombinasyonunun meydana getirdiği genotoksik hasarları geri çevirdiği sonucuna ulaşıldı. In this study, genotoxic effects of Levodopa and Carbidopa, drugs that are used in treatment Parkinson's disease, and antigenotoxic effects of uridine, a pyrimidine nucleoside, are investigated. In vivo mouse bone marrow micronucleus test and Comet assay are used for this purpose.Levodopa was administered to the mice by intraperitoneal injection at 10, 50 and 100 mg/kg doses. As a result of the mouse bone marrow micronucleus assay after 24 hours of treatment, the ratio of polychromatic erythrocyte with micronucleus increased significantly in all of the three dose groups compared to the control group. According to Comet assay results, an increase in Comet tail length, tail DNA percentage, DNA damage index and percentage of damaged cells in a dose dependent manner and a statistical decrease in head DNA percentage were determined in Levodopa treatment groups.Carbidopa administered to the mice by intraperitoneal injection at 1, 5 and 10 mg/kg doses had no genotoxic effects.Levodopa and Carbidopa were administered in combination to the mice by intraperitoneal injection at 10/1, 50/5 and 100/10 mg/kg doses. As a result of in vivo mouse bone marrow micronucleus assay and Comet assay, increase in the ratio of polychromatic erythrocyte with micronucleus in 50/5 and 100/10 mg/kg dose groups was statistically significant compared to the control group (p < 0,0001). According to Comet assay results, there was a statistically significant increase in Comet tail lengths in 50/5 and 100/10 mg/kg dose groups in combination treatment compared to negative control group. Increase in tail DNA percentage in all three dose groups, decrease in head DNA percentage with increasing doses and increase in DNA damage index values in all three dose groups were statistically significant compared to negative control. It was also found that increase in the percentage of damaged cells compared to control group in 50/5 and 100/10 mg/kg dose groups was statistically significant.According to Comet assay and in vivo micronucleus assay, Uridine treatment at 100 mg/kg dose had no genotoxic effect. Combination of Uridine with 10, 50 and 100 mg/kg doses of Levodopa decreased the ratio of polychromatic erythrocyte with micronucleus 1,8-, 2,15- and 2,85-fold respectively. The same combination decreased Comet tail lengths 2,09-, 2,69- and 4,94-fold respectively and decreased genetic damage index values 2,59-, 6,64- and 6,18-fold respectively.According to Comet assay and in vivo mouse bone marrow micronucleus assay performed with Uridine at 100 mg/kg dose and Levodopa/Carbidopa combination at 10/1, 50/5 and 100/10 mg/kg doses, administered Uridine dose decreased the ratio of polychromatic erythrocyte with micronucleus 1,03-, 2,37- and 3,83 -fold, the ratio of Comet tail lengths 2,35-, 3,43- and 4,29-fold, the ratio of tail DNA percentage 5,73-, 15,74- and 17,13-fold, the ratio of genetic damage index 3,23-, 5,73- and 5,93-fold respectively and the ratio of percentage of damaged cells, which would in turn arise from Levodopa/Carbidopa combination doses.In conclusion, genotoxic effects of the drugs, Levodopa and Carbidopa are studied by using in vivo mouse bone marrow micronucleus test and Comet assay and it was found that Carbidopa treatment alone has no genotoxic effect. A statistically significant increase in micronucleus frequency was determined as a result of the treatment with Levodopa alone and its combination with Carbidopa (p < 0,0001). It was concluded that Uridine had no genotoxic effect; furthermore it reverts the genotoxic damage caused by Levodopa/Carbidopa combination when it is used in combination with these agents.

There is an increasing demand for natural antioxidant molecules in order to replace the synthetic additives in the food industry. Therefore, Ulva rigida C. Agardh was analyzed to determine its bioactive components, including the total phenolic content, antioxidant capacity (lipid and water-soluble), vitamins (A, E, and C), protein, carbohydrate, and pigments. As a result, Ulva rigida showed a high total phenolic, vitamin E, and total carotene content. Hence, U. rigida could be considered as a plant possessing natural antioxidant molecules and might be useful for the food industry. U. rigida can also be used for curing diseases arising from oxidative deterioration.

A 2-year-old, female Persian cat was presented with a history of distocia. In her first pregnancy, she had whelped four kittens and had eaten all of them right after parturition. She had mated again with the same tomcat. Well-developed foetuses with weak foetal heart beats were observed in the ultrasonographic examination. En block ovariohysterectomy was performed. Three live and mature foetuses were obtained from the uterus; two of them were female foetuses and had no anatomical problem but the third one exhibiting multiple malformations was a male and diagnosed as 'schistosoma reflexum' (SR). The vertebral column deviated markedly to the right (scoliosis) at thoracolumbar region, and the middle lumbar and the sacral vertebrae were directed dorsocranially (lordosis). The entire small intestine, a part of large intestine, stomach, spleen and the right kidney were displayed out of the body, and it seemed that the listed internal organs were protruded from an abdominal cleft associated with the allantoic membrane. Liver, lungs and heart were hypoplastic. The large intestine was seen to have blind end (atresia recti), but anus was normal. Cerebrum and cerebellum were noticed as normal in sizes. Chromosome preparations from lymphocyte cultures of the foetus showed chromosomal aberrations including chromatid and chromosome breaks, exchange figures, non-homologous pairing, whereas no abnormalities were detected in the chromosome preparations from mother's cultures. This is probably the first case of SR in a cat, which was examined in detail from clinical, pathological, radiological and chromosomal angles.

This study was designed to investigate the effects of Ulva rigida, one of the green algae, on the lipid profile and oxidative–antioxidative systems in streptozotocin-induced diabetic rats. Forty Wistar rats randomly divided into four groups: control (C), control + U. rigida extract (C + URE), diabetes (D) and diabetes + U. rigida extract (D + URE). U. rigida (2%) was administered in drinking water for 5 weeks after the induction of diabetes. U. rigida reduced the blood glucose, serum total cholesterol, triglyceride levels and plasma and tissue malondialdehyde (MDA) levels in the D + URE group. Insulin levels were significantly higher in the D + URE than those of the D group. Serum total cholesterol and tissue MDA levels were reduced in the C + URE group. Whole blood glutathione peroxidase and erythrocyte superoxide dismutase activities were higher in the D and C + URE groups compared with the C group. Paraoxonase and arylesterase activities were lower in the D group while U. rigida increased paraoxonase activities in C + URE and D + URE groups. This is the first study which showed U. rigida has antidiabetic and antihyperlipidemic effects and improves oxidative stress in diabetic rats. We conclude that U. rigida might have a potential use as a protective and/or therapeutic agent in diabetes mellitus. Copyright © 2011 John Wiley & Sons, Ltd.

Several hazardous substances, can damage our DNA in various ways. Defining these substances and the protective ones is very important. Therefore, researches have increased on various compounds based on natural sources which keep the harmful effects of these various agents at the minimum level. In the present study, we evaluated the potential genotoxic/ antigenotoxic/ antimutagenic activity of the crude chloroform: methanol (2:1) extracts of Hypnea musciformis (Wulfen) Lamouroux (HME), in human lymphocytes culture in vitro against genotoxic/ mutagenic agents mitomycin C (MMC) and ethyl methanesulfonate (EMS) by using chromosome aberration (CA), sister chromatid exchange (SCE) and micronuclei (MN) assays, and also determined total antioxidant capacity (in soluble lipid and water), phenolic compound, protein, carbohydrate, vitamins (A, C and E) contents. The frequency of chromosome aberrations and SCE increased by MMC, were significantly decreased by HME (p < 0.05 for CA, p < 0.001 for SCE). The MN frequencies of the cells were significantly decreased by the treatment with HME plus MMC or EMS when compared with the positive controls (MMC or EMS) (p < 0.05). In conclusion, HME itself is not a clastogenic or cytotoxic substance. On the other hand, HME possesses a strong antigenotoxic, anti-clastogenic and protective effects against MMC in vitro.

A cytogenetic monitoring study was carried out on a group of workers from transformer and distribution line stations in the Bursa province of Turkey, to investigate the genotoxic risk of occupational exposure to extremely low frequency electric (ELF) and magnetic fields (EMF). Cytogenetic analysis, namely chromosomal aberrations (CAs) and micronucleus (MN) tests were performed on a strictly selected group of 55 workers and compared to 17 controls. CA and MN frequencies in electrical workers appeared significantly higher than in controls (p < 0.001, 0.05, respectively). The frequency of CA in exposed groups were significantly enhanced with the years of exposure (p < 0.01). The effect of smoking on the level of CA and MN was not significant in the control and exposure groups. The results of this study demonstrated that a significant induction of cytogenetic damage in peripheral lymphocytes of workers engaged to occupational exposure to ELMF in electric transformer and distribution stations.

An increased reactive oxygen species (ROS) and insufficient antioxidant activity is known in diabetes mellitus (DM). Antioxidant compounds in the human foods or supplementary diets can be used to counteract several diseases. The analysis of micronuclei (MN) is a cytogenetic technique used to show chromosomal damage caused by clastogenic affects. The present study was designed to evaluate: (i) the effects of diabetes mellitus on bone marrow MN frequency, (ii) the effect of oral administration of Ulva rigida ethanolic extract (URE) on MN frequency produced by DM, and (iii) some hematological values in normal and streptozotocin-induced diabetic rats. Daily fluid and food consumptions, weekly body weights, blood glucose concentrations and serum insulin levels were also examined in the study groups during the two different administration periods. The blood glucose concentration and MN frequency have been significantly increased in diabetic rats compared with the normal rats (p < 0.0001). Especially, URE-30d group treatment in diabetic rats was significantly decreased blood glucose concentrations and MN frequency. This is the first report on the anti-hyperglycemic, anti-oxidative and genotoxic/antigenotoxic capacity of U. rigida in vivo. Our results suggest that URE shows strong anti-hyperglycemic and antigenotoxic effect on the genotoxicity produced by DM in rats.

Oxidative stress-induced DNA damage seems to play a role in the pathogenesis of type-1 diabetes mellitus and its complications. Several in vitro assays have been used to measure the DNA damage produced by oxidative stress. In the present study, we aimed to investigate the frequency of sister chromatid exchange (SCE), chromosomal aberrations (CA) and micronuclei (MN) in type-1 diabetes mellitus patients compared with healthy controls. SCE. CA and MN tests were carried out with the blood-cell cultures from 35 type-1 diabetic patients and 15 healthy, age- and sex-matched control subjects. The mean age of the type-1 diabetic patients was 31.89 +/- 10.01 years, with a mean duration of the diabetes of 7.8 +/- 6.02 years. The mean level of HbA1c of the type-1 diabetic patients was 8.37 +/- 1.36%. Only three (8.5%) patients with type-1 diabetes mellitus had an HbA1c level below 7%. Patients with type-1 diabetes mellitus showed a higher frequency of SCE compared with controls (5.44 +/- 1.47 and 2.54 +/- 0.82, respectively, p < 0.001). but there was no significant correlation between the duration of diabetes, HbA1c and SCE. No significant difference was found in CA or MN frequency in type-1 diabetic patients compared with controls. In conclusion, these results suggest that type-1 diabetes mellitus is a condition with genomic instability characterized by an increased level of SCE. Hyperglycemia-induced oxidative stress may be the underlying factor of the increased SCE frequency.

Objective To determine the in vitro possible clastogenic and cytotoxic activities of Ova rigida crude extracts (URE), and identify their antigenotoxic and protective effects on chemotherapeutic agent mitomycine-C (MMC). Methods Anti-clastogenic and anti-genotoxic activities of Ulva rigida crude extracts (URE) were studied using chromosome aberration (CA), sister chromatid exchange (SCE), and micronuclei (MN) tests in human lymphocytes cultured in vitro. Results The chromosome aberration, sister chromatid exchange or micronuclei tests showed that URE at concentrations of 10, 20, and 40 mu g/mL had no clastogenic activity in human lymphocyte cell Culture. Three doses of URE significantly decreased the number of chromosomal aberrations and the frequencies of SCE and MN when compared with the culture treated with MMC (P

4, 6-Dinitro-o-cresol (DNOC) is a pesticide, fungicide and insecticide, used in agriculture. In this research the genotoxic effect of DNOC on the root tips of Allium cepa L. was determined. The correlations between the effects of different concentrations, exposure times on the mitotic index (MI) and induction of chromosomal aberrations (CA) were also examined. Experiments were carried out in duplicate, using aqueous solutions of DNOC to concentrations of 250 and 500 ppm, at intervals of 0, 3, 6, 12, and 24 h. The results revealed an inhibition of the MI at the highest concentration and experiment times; this is an evidence of cytotoxicity of DNOC. Large number of c-mitosis indicated that DNOC acts as a strong spindle inhibitor, whereas, other CA types such as, breaks, bridges etc. were found in all tested concentration and times (p < 0.001) showing that is a potent clastogen.

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.