Genotoxicity of the some selective estrogen receptor modulators: a review

The objective of this article is to review genotoxicological profile of the major selective estrogen receptor modulators, including clomiphene, tamoxifen, toremifene, raloxifene. These drugs have been used for infertility treatment and breast cancer prevention in high risk-women. However, some studies reported that especially tamoxifen is a genotoxic agent and is related with endometrial cancer. Our review indicate that clomiphene and tamoxifen were found as genotoxic agent in majority of the tests. However published reports showed that toremifene is a weakly genotoxic agent. The genotoxic effects of raloxifene are still poorly known. Further genotoxicity studies should be conducted especially for raloxifene.     

Abnormal expression, localization and interaction of canonical transient receptor potential ion channels in human breast cancer cell lines and tissues: a potential target for breast cancer diagnosis and therapy

Background  

Ca²⁺ is known to be involved in a number of metastatic processes including motility and proliferation which can result in store-depletion of Ca²⁺. Up regulation of genes which contribute to store operated channel (SOC) activity may plausibly be necessary for these processes to take place efficiently. TRPC proteins constitute a family of conserved Ca²⁺-permeable channels that have been shown to contribute to SOC activity.     

Evaluation of Some Phenological and Biochemical Characteristics of Selected New Late Flowering Dried Apricot Cultivars

In this study, promising candidates of six apricot genotypes were compared with our local and major cultivar (Hac?halilo?lu) based on their phenological, pomological, and biochemical characteristics. Fruit weight, stone weight, flesh firmness, flesh fruit/stone ratio, TSS (Total soluble solids), glucose, fructose, sucrose, total phenols, total antioxidant activity (FRAP and ABTS assays) and bud break, first bloom, full bloom, and harvesting date of apricot cultivar candidates were compared with cultivar Hac?halilo?lu ‘HH.’ According to the obtained results, the higher content of total phenolic compounds and total antioxidant activity was determined in the N95 genotype (96.87 µmol TE/g) fruit, whereas the ‘HH’ cultivar was characterized by the lower value (94.6 µmol TE/g) especially determined by FRAP method. Individual sugars and the soluble solids content of fruit differed between selected genotypes and ‘HH’ cultivar. Glucose, fructose, and sucrose contents were higher in all selected genotypes than in Hac?halilo?lu cultivar.     

Effects of aminoguanidine and antioxidant erdosteine on bleomycin-induced lung fibrosis in rats.

Reactive oxygen and nitrogen species have been implicated in the pathogenesis of bleomycin-induced lung fibrosis. The effects of aminoguanidine and erdosteine on the bleomycin-induced lung fibrosis were evaluated in rats. The animals were placed into five groups: Vehicle + vehicle, vehicle + bleomycin (2.5 U/kg), bleomycin + aminoguanidine (200 mg/kg), bleomycin + erdosteine (10 mg/kg), and bleomycin + erdosteine + aminoguanidine. Bleomycin administration resulted in prominent lung fibrosis as measured by lung hydroxyproline content and lung histology, which is completely prevented by erdosteine and aminoguanidine. A strong staining for nitro tyrosine antibody in lung tissue and increased levels of lung NO were found in bleomycin group, that were significantly reduced by aminoguanidine and erdosteine. Aminoguanidine and erdosteine significantly prevented depletion of superoxide dismutase and glutathione peroxidase and elevated myeloperoxidase activities, malondialdehyde level in lung tissue produced by bleomycin. Data presented here indicate that aminoguanidine and erdosteine prevented bleomycin-induced lung fibrosis and that nitric oxide mediated tyrosine nitration of proteins plays a significant role in the pathogenesis of bleomycin-induced lung fibrosis. Also our data suggest that antifibrotic affect of antioxidants may be due to their inhibitory effect on nitric oxide generation in this model.     

Development and linkage mapping of novel sex-linked markers for marker-assisted cultivar breeding in pistachio (<Emphasis Type="Italic">Pistacia vera</Emphasis> L.)

The dioecious character of Pistacia vera L (the pistachio tree) limits its breeding capacity. Thus, early stage selection of males can save time, labor, and land. This study aimed to develop sex-linked single nucleotide polymorphism (SNP) markers, together with expressed sequence tag-derived simple sequence repeats (EST-SSRs), to determine position of the sex locus in pistachio by constructing a linkage map of its sex chromosome for the first time. Nine novel sex-linked SNP markers were successfully identified by SNaPshot minisequencing analysis of 25 SNP loci from 17 restriction site-associated DNA (RAD) reads in 309 individuals. All nine markers were heterozygous in females and homozygous in males supporting a ZW/ZZ sex determination system in pistachio. A total of 105 segregating SSRs and sex-linked markers were used to identify the sex chromosome and the position of the sex locus through analysis of a Siirt × Ba?yolu F₁ population with 122 progenies. Of these 105 markers, four common and four paternal SSRs were mapped onto the sex chromosome, along with the phenotypic sex locus and sex-linked markers. The resulting consensus map had a total length of 65.19 cM. The sex locus and sex-linked SNP markers were located in the center of the chromosome at a distance of 31.86 and 31.92 cM, respectively. This study presents valuable information about the sex chromosome and sex locus position as well as novel polymorphic EST-SSRs and nine sex-linked SNP markers in pistachio.     

Caffeic Acid Phenethyl Ester Exerts a Neuroprotective Effect on CNS Against Pentylenetetrazol-Induced Seizures in Mice

Since overexcitation of excitatory amino acid is an important mechanism in seizure genesis wherein free radicals have recently been suggested to play a critical role, we explored the effects of caffeic acid phenethyl ester (CAPE) administration in pentylenetetrazole (PTZ)-induced seizure in mice. CAPE prevents the oxidative damage in brain tissue induced by PTZ, scavenging reactive oxygen species (ROS). Our results demonstrate that CAPE treatment which prevents free radical production and ameliorates seizure severity may be useful at least as an adjunctive treatment of seizure disorders.     

fruitless splicing specifies male courtship behavior in Drosophila

All animals exhibit innate behaviors that are specified during their development. Drosophila melanogaster males (but not females) perform an elaborate and innate courtship ritual directed toward females (but not males). Male courtship requires products of the fruitless (fru) gene, which is spliced differently in males and females. We have generated alleles of fru that are constitutively spliced in either the male or the female mode. We show that male splicing is essential for male courtship behavior and sexual orientation. More importantly, male splicing is also sufficient to generate male behavior in otherwise normal females. These females direct their courtship toward other females (or males engineered to produce female pheromones). The splicing of a single neuronal gene thus specifies essentially all aspects of a complex innate behavior.     

Optimization of ethanol production using newly isolated ethanologenic yeasts

Yeasts are important microorganisms used for ethanol production; however, they are not equally efficient in the amount of ethanol production under different environmental conditions. It is, therefore, necessary to screen for elite strains to utilize them for commercial production of these commodities. In this study, yeasts were isolated from different Ethiopian traditional fermented alcoholic beverages (teji, tella, shamiata and areqe tinisis), milk and ergo, teff and maize dough, soil and compost, flowers, and fruits to evaluate their potential use for ethanol fermentation process. Isolates were screened for efficient ethanol production and the selected ones were identified using phenotypic and genetic characters using D1/D2 region of LSU rDNA sequence analysis. The yeast isolates were evaluated based on their growth and fermentation of different carbon sources. Response surface methodology (RSM) was applied to optimize temperature, pH and incubation time using central composite design (CCD) in Design-Expert 7.0.0. A total of 211 yeasts colonies were isolated of which 60% were ethanologenic yeasts (ethanol producers) and 40% were non-ethanol producers. The yeast population detected from various sources was in the range of 10⁵ CFU from traditional foods and beverages to that of 10³ CFU from fruits and soil samples. The data also showed that the number of colony types (diversity) did not correlate with population density. The highly fermentative isolates were taxonomically characterized into four genera, of which 65% of the isolates (ETP37, ETP50; ETP53, ETP89, ETP94) were categorized under Saccharomyces cerevisiae, and the remaining were Pichia fermentans ETP22, Kluyveromyces marxianus ETP87, and Candida humilis ETP122. The S. cerevisiae isolates produced ethanol (7.6-9.0 g/L) similar with K. marxianus ETP87 producing 7.97 g/L; comparable to the ethanol produced from commercial baker's yeast (8.43 g/L) from 20 g/L dextrose; whereas C. humilis ETP122 and P. fermentans ETP22 produced 5.37 g/L and 6.43 g/L ethanol, respectively. S. cerevisiae ETP53, K. marxianus ETP87, P. fermentans ETP22 and C. humilis ETP122 tolerated 10% extraneous ethanol but the percentage of ethanol tolerance considerably decreased upon 15%. S. cerevisiae ETP53 produced ethanol optimally at pH 5.0, 60 h, and 34^oC. pH 4.8, temperature 36^oC, and 65 h of time were optimal growth conditions of ethanol fermentation by K. marxianus ETP87. The ethanol fermentation conditions of P. fermentans ETP22 was similar to S. cerevisiae ETP53 though the ethanol titer of S. cerevisiae ETP53 was higher than P. fermentans ETP22. Therefore, S. cerevisiae ETP53, K. marxianus and P. fermentans ETP22 are good candidates for ethanol production.