Investigation of genotoxic effects of doripenem using cytogenetic and molecular methods.

The main aim of this study was to investigate the genotoxic effects of doripenem (DRP) using both cytogenetic and molecular test systems. Although there have been some studies reporting the effects of DRP, none of them has shown the genotoxic effects of DRP. In order to achieve the main aim of the study, the human peripheral lymphocytes were treated with 100 µg/ml, 200 µg/ml, and 400 µg/ml concentrations of DRP for 24 and 48 hours, and the chromosome aberration (CA) and micronucleus (MN) methods were used as the cytogenetic tests and RAPD-PCR method was used as the molecular test to determine the genotoxic effects of DRP. DRP did not induce the chromosome aberrations and micronucleus frequencies at all concentrations and at all treatment periods. So, it was concluded that DRP did not show any cytotoxic effect. However, DRP increased the number of polymorphic bands and decreased the ratio of genomic template stability, especially at the 48-hour treatment period. In this study, according to the obtained results, it was determined that DRP failed to show any genotoxic risk at the therapeutic doses. This result also indicates that DRP could be a reliable antibiotics according to its rapid metabolism.

Alterations on high HbF levels may be associated with KLF1 gene mutations.

The KLF1 gene synthesizes a transcription factor in the zinc finger structure that regulates the transcription of ß-, γ-globin, and Foxm1 genes. This factor plays an important role in the erythropoiesis mechanism by modifying the chromatin structure and is involved in the regulation of transcription in the opening of the ß-globin gene. ß-globin gene expression could be disrupted by a mutation, which may be a possible cause of a disruption in regulation of the promotor of the ß-globin gene where the KLF1 transcription factor binds. This can lead to an inherited high fetal hemoglobin (HbF) ratio in people. Therefore, the main aim of this study was to determine the effects of KLF1 mutations on these high levels of HbF. In this study, in order to determine the relationship between the KLF1 mutations and the high HbF levels three exons along with the 5'-UTR and 3'-UTR regions of the KLF1 gene were sequenced of 53 volunteers. In this study, 3 variations in the non-coding regions of the KLF1 gene were not associated with a high level of HbF. Five variations were detected in the second exon of KLF1 gene. One of these is a frame shift that occurs when GG bases are inserted between the 59-60 codons, and the other four variations occur as a base substitution variations.  No correlation was found between high HbF levels and neutral variants. Only polar-nonpolar amino acid changes were found at two points. At one of them, a significant drop in the high HbF levels was observed, while the other was observed to be high near to the critical limit. These findings suggested that variations in function of the KLF1 gene can alter the HbF levels.

A biomonitoring study on the workers from textile dyeing plants.

We evaluated the genotoxic risk of workers from textile dyeing plants in Kahramanmaras, Turkey. Sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) were investigated in peripheral blood lymphocyte cultures of 40 workers and compared to those of 32 age-sex- and habit-matched healthy controls. Groups were selected after a questionnaire administration. Use of Maras powder (a kind of smokeless tobacco) was considered as modulating factor. The SCEs level did not show significant differences between workers and controls. The frequency of CA was significantly higher in workers than in controls. Use of Maras powder was a significant factor to increase the frequencies of SCE and CA in control group. The level of SCE and CA did not correlate with the age whereas there was a significant correlation between years of exposure and CA frequency. The results of this study revealed the genotoxic risk of textile dyers. Protective measures such as masks and gloves are desirable for preventing or minimizing the occupational exposure.

The mutagenic and anti-mutagenic effects of Ecballium elaterium fruit juice in human peripheral lymphocytes.

The aim of this study was to investigate the mutagenic and anti-mutagenic effects of Ecballium elaterium (EE) fruit juice which has an anti inflammatory effect using in vitro human peripheral lymphocytes. For the investigating the mutagenic effects of EE fruit juice, human peripheral lymphocytes was treated with three doses (18, 36 and 72 microl/1) of fruit juice alone for 24 and 48 h. For the investigating the anti-mutagenic effects of the EE fruit juice, the human lymphocytes also treated with the mixture of the fruit juice and 0.25 microg/ml MMC. EE fruit juice induced the percentage of total CA when used alone (especially the percentage of structural CA than the percentage of the numerical CA) and synergically induced the percentage of total CA when used as a mixture with MMC. EE fruit juice did not affect the SCE frequency for 24 and 48 h treatment time. In contrast, EE and MMC as a mixture, sinergically induced the SCE frequency at the highest concentration for 48 h treatment time only. EE alone did not decrease the RI while it decreased the MI as a dose dependent manner. EE and MMC as a mixture have the higher cytotoxic effect than the cytotoxic effects of EE alone. As a result, it can be concluded that, EE had no anti-mutagenic effect while EE had a mutagenic and a cytotoxic effect in human peripheral lymphocytes.

Chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes treated with sodium metabisulfite, a food preservative.

The aim of this study was to investigate the ability of sodium metabisulfite (SMB) which is used as an antimicrobial substance in food, to induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in human lymphocytes. SMB-induced CAs and SCEs at all concentrations (75, 150 and 300 microg/ml) and treatment periods (24 and 48h) dose-dependently. However, SMB decreased the replication index (RI) and the mitotic index (MI) at the concentrations of 150 and 300 microg/ml for 24 and 48h treatment periods. This decrease was dose-dependent as well.

In vivo chromosomal aberrations in bone marrow cells of rats treated with Marshal.

In this study, the cytogenetic effects of Marshal (insecticide/nematocide) were investigated in bone marrow cells of rats. The results obtained from animals treated with Marshal were compared with the results of animals treated with ethyl carbamate (EC) and with controls. Concentrations of 12.5, 25 and 50 mg/kg b.wt. of Marshal and 100, 200 and 400 mg/kg b.wt. of EC were used and animals were sampled at three different times (6, 12 and 24 h). Marshal increased the number of chromosomal aberrations (CA) per cell, and the number of cells with abnormalities, at all concentrations and treatment times. Generally, Marshal could increase the number of the abnormal cells and the formation of CA as easily as EC. However, Marshal, at 50 mg/kg b.wt. did not increase the frequency of abnormal cells or CA as strongly as EC, at 400 mg/kg b.wt. for 6 h. Marshal also decreased the mitotic index (MI) compared with the control group. The MI was higher in the group treated with Marshal for 6 h than that treated with EC. However, the effects of Marshal and EC on the MI in the groups treated for 12 and 24 h were similar. We found that the effect of Marshal on the formation of abnormal cells and CA was dependent on concentration and treatment time.