Investigation of DPYD, MTHFR and TYMS polymorphisms on 5-fluorouracil related toxicities in colorectal cancer.

Aim: To investigate the association of DPYD, MTHFR and TYMS polymorphisms on 5-fluorouracil (5-FU) related toxicities and patient survival. Materials & methods: A total of 103 colorectal cancer patients prescribed 5-FU were included in the study. Genotyping was conducted for several DPYD, MTHFR and TYMS polymorphisms using a microarray analyzer. Results: DPYD 496A>G polymorphism was found to be significantly associated with 5-FU related grade 0-2, but not severe toxicities (p = 0.02). Furthermore, patients with DPYD 85TC and CC genotypes had longer progression and overall survival times compared to TT genotypes in our study group (log rank = 6.60; p = 0.01 and log rank = 4.40; p = 0.04, respectively). Conclusion: According to our results, DPYD 496AG and GG genotypes might be protective against severe adverse events compared to the AA genotype. Another DPYD polymorphism, 85T>C, may be useful in colorectal cancer prognosis. Further studies for both polymorphisms should be conducted in larger populations to achieve accurate results.

5-fluorouracil (5-FU) is a widely used drug for chemotherapy in colorectal cancer. In this study, we investigated the relationship between the severity of 5-FU induced adverse events and several variations in DPYD, MTHFR and TYMS genes, which encode the enzymes involved in 5-FU metabolism in a total of 103 colorectal patients. We also examined the relationship between the polymorphisms and progression-free and overall survival times of the patients in our study group. Among the variations, DPDY 496A>G polymorphism was found to be associated with 5-FU induced adverse events. Also, the DPYD 85T>C polymorphism was detected to be associated with longer progression-free and overall survival times.

The effects of glipizide on DNA damage and nuclear transport in differentiated 3T3-L1 adipocytes.

BACKGROUND: Despite commonly use for treatment of type II diabetes, possible effects of glipizide on nuclear transport and DNA damage in cells are unknown. Since clinical response of glipizide may change with aging, the aim of the study was to investigate the effect of glipizide by comparing mature and senescent adipocytes. METHODS AND RESULTS: The effects of glipizide were investigated in 3T3-L1 adipocytes. Effective and lethal doses were determined by real-time monitoring iCELLigence system. Comet assay was performed to determine DNA damage and quantitative PCR was conducted to detect gene expression levels. RAN expressions were found to be up regulated in mature 180 µM glipizide treated adipocytes compared to control group (p < 0.05); whereas down regulated in senescent 180 µM glipizide treated adipocytes compared to their control adipocytes (p < 0.05). Olive Tail Moment values were significantly higher in mature 180 µM glipizide treated adipocytes (MTG) and senescent 180 µM glipizide treated adipocytes (STG) comparing their untreated controls (p < 0.001 and p < 0.001 respectively). Also class 5 comets that shows severe DNA damage were found to be higher in both MTG and STG groups than their controls (p < 0.001 and p < 0.001, respectively). OTM values were higher in STG than MTG (p < 0.001). CONCLUSIONS: This is the first study that reports glipizide caused DNA damage increasing with senescence in adipocytes. As a response to glipizide treatment Ran gene expression increased in mature; and decreased in senescent adipocytes. Further studies are needed to reveal the effect of glipizide on DNA and nuclear interactions in molecular level.

Alterations in niban gene expression as a response to stress conditions in 3T3-L1 adipocytes.

Adipocyte death is important in obesity development. Understanding and prevention of adipocyte deaths may be a molecular approach in the treatment. In the study, we aimed to understand role of Niban gene, which acts as an anti-apoptotic molecule as a response to stress conditions, in adipocytes. 3T3-L1 adipocytes were treated with different doses of linoleic acid, hydrogen peroxide and ethanol; and proliferation of the cells examined with real time monitoring iCELLingence system. Gene expression levels were measured by q-PCR. As a response to 24h 480 µM linoleic acid treatment, Niban gene expression was found to be higher than control group (p = 0.008), whereas 24 h 90 mM ethanol treatment was determined to be lower than control group (p = 0.008). The highest value of Niban gene expression among H2O2 treatment groups was detected in 4h 600µM H2O2 in comparison to control group (p = 0.008). To understand role of Niban in adipogenesis, Niban gene expressions were compared between pre-adipocytes and advanced fat accumulated adipocytes and determined to be significantly different (p = 0.042). Our results suggest that Niban might be involved in stress response process in adipocytes. However, the exact molecular role of Niban needs to be investigated in further studies.

Evaluation of Cytotoxicity and Mutagenicity of Wastewater from Istanbul: Data from Hospitals and Advanced Wastewater Treatment Plant.

Wastewater (WW) carry considerable amount of chemicals that could have mutagenic or cytotoxic effect from hospital discharges to aquatic environment. Our objective was to determinate the possible mutagenic and toxic effects of hospital originated WWs and effectiveness of the wastewater treatment plants (WTP) functions. In the study the mutagenic and cytotoxic potential of three hospitals and influent/effluent of a treatment plant WW collected in Istanbul and was examined using AMES, XTT, and lactate dehydrogenase (LDH) assays. Mutagenic effects were detected at both hospital discharges and advanced biological wastewater plant. We observed no cytotoxic effect in fibroblasts for LDH and XTT assays whereas high cytotoxicity for all samples was found in hepatocytes by XTT assay. According to the results even if advanced technology is used for treatment of WW, mutagenic and cytotoxic effects still remain, and the present technologies need to be further improved.