Şükrü Öztürk

Effect of Cyclosporin A and Tacrolimus on Sister Chromatid Exchange Frequency in Renal Transplant Patients

Long-term use of Cyclosporin A (CsA) and Tacrolimus is known to yield serious untoward side effects including nephrotoxicity, neurotoxicity, and malignant tumor formation. Sister chromatid exchange (SCE) is used to assess the genotoxic potential of various agents. A total of 37 postrenal transplant patients receiving either CsA (n = 20) or Tacrolimus (n = 17) were included in this study. The genotoxic effects of CsA and Tacrolimus were assessed by determination of SCE frequency. In patients receiving CsA, SCE frequency was increased significantly compared to that in the control group (p = 0.001), whereas Tacrolimus did not yield such a significant change (p = 0.801). SCE frequency was not correlated with drug dosage (p > 0.05). Our results indicate that the use of CsA, but not Tacrolimus 506, is associated with an increased genotoxic effect in postrenal transplant patients.

The Effects of Etodolac, Nimesulid and Naproxen Sodium on the Frequency of Sister Chromatid Exchange after Enclused Third Molars Surgery

Purpose Non-steroidal anti-inflammatory drugs (NSAID) are frequently used in oral surgical procedures in dentistry. The evaluation of the frequency of sister chromatid exchange (SCE) is accepted as a reliable cytogenetic method to assess the genotoxic effects of environmental factors. Materials and Methods In this study, the genotoxic effects of various NSAIDs were assessed in 30 patients to who they were administered following encluosed third molar surgery using SCE analysis before and after the operation. The frequency of SCE was evaluated before the operation and after 3 days of etodolac, nimesulid and naproxen use. Results There was no statistically significant difference in the frequency of SCE between the preoperative and postoperative states in patients given etodolac, nimesulid or naproxen sodium. Conclusion Short term use of selective and non-selective NSAIDs was not associated with a significant genotoxic effect that could be detected using the SCE method in peripheric lymphocytes.

Sister chromatid exchange frequency in B-cells stimulated by TPA in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is characterised by the clonal proliferation and accumulation of neoplastic B-lymphocytes. The median age of the patients is 65 years, and more men than women are affected. The overwhelming majority of CLLs are of B-cell origin. Chromosomal aberrations have been detected in more than 50% of the B-cells obtained from peripheral blood samples after appropriate stimulation with polyclonal B-cell mitogens. The analysis of sister chromatid exchange is a cytogenetic technique used to show DNA damage due to an exchange of DNA fragments between sister chromatids. In this study, lymphocytes from 22 patients with CLL-B (7 female, 15 male; mean age 64.09 +/- 7.56 years) were stimulated by a B-cell mitogen (TPA) and BrdU added at the 24 h of the culture. Metaphase chromosomes were stained with a fluorescence plus Giemsa technique after a standard harvest procedure. The frequency of sister chromatid exchange was found to be increased significantly P =.02) in patients with CLL-B (8.24 +/- 1.36 per metaphase) compared to controls (7.25 +/- 1.42 per metaphase). We conclude that the increased frequency of sister chromatid exchange in chronic lymphocytic leukemia after stimulation with a B-cell mitogen (TPA) may reflect DNA instability and defective DNA repair in these patients.

A novel two bases deletion in the albumin gene causes analbuminaemia in a young Turkish man.

Fig. 1. Molecular effect of the novel c.229_230delTG. (A) Genomic DNA sequence electropherograms showing the mutation found in exon 3 of the proband. The arrow indicates the two bases that are deleted in the patient: TG at nucleotide positions c. 229–230. (B) DNA sequence and amino acid translation of a portion of exon 3 from the ALB gene for a wild-type allele [6] and the mutant Amasya allele. The underlined nucleotides indicate the two bases that are deleted in the Amasya allele. This deletion leads to a frameshift mutation that introduces a premature stop codon two amino acids downstream. Codon numbering is according to the HGVS rules, i.e. starting from the initiator codon. A novel two bases deletion in the albumin gene causes analbuminaemia in a young Turkish man

A Case of Chronic Lymphocytic Leukemia with a Constitutional Pericentric Inversion of Chromosome 1

Chronic lymphocytic leukemia (CLL) has been reported to be associated with various chromosomal aberrations, the most common being trisomy 12 and structural rearrangements involving 13q, 11q, and 17p. We present a case of CLL with a constitutional pericentric inversion of chromosome 1.

Micronuclear and sister chromatid exchange analyses in peripheral lymphocytes of patients with oral lichen planus – a pilot study*

OBJECTIVE The purpose of this study was to determine the genetic instability of peripheral blood lymphocytes from patients diagnosed with oral lichen planus (OLP) by investigation of frequencies of micronuclei (MN) and sister chromatid exchange (SCE). MATERIALS AND METHODS A total of 22 newly diagnosed and untreated patients with OLP of same severity scores and twenty healthy controls participated in this study. They were all non-smokers with no previous history or family history of cancer. The periodontal status, flow rate and buffering capacity of whole mouth saliva were recorded. SCE and MN analyses were performed on peripheral blood lymphocytes of OLP patients and healthy controls. RESULTS The frequencies of MN (50.00 +/- 22.36) and SCE (6.89 +/- 1.48) in OLP patients were found to be significantly elevated compared with that in normal individuals (25.20 +/- 9.52 and 5.93 +/- 1.31; z = 3.946, P = 0.0001; z = 2.346, P = 0.019). There were no significant differences in the MN frequency and SCE between the two subgroups with reticular or erosive types of OLP. CONCLUSION These pilot data indicate an increased genomic instability in peripheral blood lymphocytes of a cohort of Turkish patients diagnosed with oral lichen planus as compared with that of healthy individuals. As patients with OLP may have an increased or potential risk for oral malignancy, these assays could be used in translational research to monitor beneficial effects of interventions and long-term prognosis.

Investigation of Gene Expressions of Myeloma Cells in the Bone Marrow of Multiple Myeloma Patients by Transcriptome Analysis

Background: Multiple myeloma is a plasma cell dyscrasia characterized by transformation of B cells into malignant cells. Although there are data regarding the molecular pathology of multiple myeloma, the molecular mechanisms of the disease have not been fully elucidated. Aims: To investigate the gene expression profiles in bone marrow myeloma cells via RNA-sequencing technology. Study Design: Cell study. Methods: Myeloma cells from four patients with untreated multiple myeloma and B cells from the bone marrow of four healthy donors were sorted using a FACSAria II flow cytometer. The patient pool of myeloma cells and the control pool of B cells were the two comparative groups. A transcriptome analysis was performed and the results were analyzed using bioinformatics tools. Results: In total, 18.806 transcripts (94.4%) were detected in the pooled multiple myeloma patient cells. A total of 992 regions were detected as new exon candidates or alternative splicing regions. In addition, 490 mutations (deletions or insertions), 1.397 single nucleotide variations, 415 fusion transcripts, 132 frameshift mutations, and 983 fusions, which were reported before in the National Center for Biotechnology Information, were detected with unknown functions in patients. A total of 35.268 transcripts were obtained (71%) (25.355 transcripts were defined previously) in the control pool. In this preliminary study, the first 50 genes were analyzed with the MSigDB, Enrichr, and Panther gene set enrichment analysis programs. The molecular functions, cellular components, pathways, and biological processes of the genes were obtained and statistical values were determined using bioinformatics tools and are presented as a supplemental file. Conclusion: EEF1G, ITM2C, FTL, CLPTM1L, and CYBA are identified as possible candidate genes associated with myelomagenesis.