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Open access

Ayse Engin, Bensu Karahalil, Ali Karakaya and Atilla Engin

Association Between XRCC1 ARG399GLN and P53 ARG72PRO Polymorphisms and the Risk of Gastric and Colorectal Cancer in Turkish Population

Gastric cancer is one of the most common cancers of the gastrointestinal system, and its overall five-year survival rate is still 15 % to 20 %, as it can mostly be diagnosed at an advanced stage. On the other hand, although colorectal cancer has a rather good prognosis, mortality is one half that of the incidence.

As carcinogenesis is believed to involve reactive radicals that cause DNA adduct formation, impaired repair activity, and weakened tumour suppression, it would help to understand the role of the polymorphisms of nucleotide excision repair enzyme XRCC1 and of tumour suppressor gene p53 in gastric and colorectal cancers. Our study included 94 gastric cancer patients, 96 colorectal cancer patients, and 108 cancer-free individuals as control with the aim to see if there was an association between XRCC1 Arg399Gln and p53 Arg72Pro polymorphisms and cancer susceptibility. DNA was extracted from peripheral blood cells and genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism. Polymorphism p53 Arg72Pro was not associated with either gastric or colorectal carcinoma, while XRCC1 Arg399Gln was not associated with the increased risk of colorectal cancer. However, XRCC1 homozygous Gln allele at codon 399 was associated with 2.54 times higher risk of gastric cancer.

Open access

Aylin Elkama and Bensu Karahalil

Abstract

Multiple sclerosis (MS) is a complex inflammatory disease of the central nervous system (CNS) resulting in neurological impairment and disability. There is evidence that adequate vitamin D levels may lower the risk of MS development. The aetiology of MS is complex and involves both genetic and environmental factors. In fact, not one but several genes are believed to lead to the disease. As for environmental factors, one of the most important risk factors is vitamin D deficiency, which, in turn, is closely related to gene polymorphisms that play a role in vitamin D metabolism and regulation. However, information about these gene polymorphisms is quite contradictory. The aim of this review is to discuss the association between some of the vitamin D-related gene variants and MS.

Open access

Hülya Türkan, Ahmet Aydin, Ahmet Sayal, Ayşe Eken, Cemal Akay and Bensu Karahalil

Oxidative and Antioxidative Effects of Desflurane and Sevoflurane on Rat Tissue in Vivo

General anaesthetics are often used in patients who are under oxidative stress due to a critical illness or surgical trauma. Some anaesthetics may worsen oxidative stress and some may act as antioxidants. The aim of this study was to evaluate liver, brain, kidney, and lung tissue oxidative stress in rats exposed to desflurane and sevoflurane and in unexposed rats. The animals were divided in three groups: control (received only air); sevoflurane (8 %), and desflurane (4 %). After four hours of exposure, we evaluated the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Cu, and Zn. Exposure to either of the anaesthetics significantly increased lung MDA levels compared to control (Mann-Whitney U test; P<0.05), probably because it is the tissue directly exposed to anaesthetic gases. Oxidative stress and antioxidant activity in other tissues varied between the desflurane and sevoflurane groups. Our results suggest that anaesthesiologist should not only be aware of the oxidative or antioxidative potential of anaesthetics they use, but should also base their choices on organs which are the most affected by their oxidative action.

Open access

Bensu Karahalil, Emine Hare, Göksel Koç, İrem Uslu, Kerem Şentürk and Yağmur Özkan

Abstract

Treatment with statins is known all over the world. They are generally considered safe at therapeutic doses. Nevertheless, clinical trials are not enough to assess their scarce adverse effects such as idiosyncratic drug induced liver injury (DILI). Due to some conditions, such as concomitant usage (drug-drug interaction using an identical metabolising enzyme) and genetic polymorphisms, there is an increasing concern about their safety. Hepatotoxicity and rhabdomyolysis have begun to appear in published studies. Most of investigations have focused on both these adverse effects and mechanisms of drug induced toxicity. The present review has attempted to compile almost all of the existing studies on the hepatotoxicity of statins but not rhabdomyolysis. The aim of our study is to provide an overview of the studies on the statin-associated hepatotoxicity and to discuss the published studies. The researchers are of the opinion that the research on this topic is incomplete but extremely necessary.

Open access

Bensu Karahalil, Esra Emerce, Bülent Koçer, Serdar Han, Necati Alkiş and Ali Karakaya

The Association of OGG1 Ser326Cys Polymorphism and Urinary 8-OHdG Levels With Lung Cancer Susceptibility: A Hospital-Based Case-Control Study in Turkey

High incidence and poor prognosis of lung cancer make it a major health problem worldwide. Although smoking is a major cause of lung cancer, only some smokers develop lung cancer, which suggests that there is a genetic predisposition in some individuals. 8-OHG is an important oxidative base lesion and may elevate due to cancer and smoking. It is repaired by 8-hydroxyguanine DNA glycosylase 1 (OGG1), which has several polymorphisms. Although the Ser326Cys polymorphism is consistently associated with a range of cancers, findings about this polymorphism and lung cancer risk are contradictory. To date, no study has examined this association in the Turkish population. We conducted a case-control study to investigate the association between OGG1 Ser326Cys polymorphism and the risk of lung cancer using PCR-RFLP. We also evaluated gene-smoking interaction and excretion of urinary 8-OHdG. Our results suggest that the OGG1 Ser326Cys polymorphism is not a genetic risk factor for lung cancer, and that the heterozygous genotype is associated with a significantly reduced risk for lung cancer. The levels of 8-OHdG did not correlate with the polymorphism and smoking. Larger association studies are needed to validate our findings, and mechanistic studies are needed to elucidate the underlying molecular mechanisms of this association.

Open access

Bensu Karahalil, Tulin Gumus, Esra Emerce, Seval Izdes, Orhan Kanbak and Elvin Kesimci

Comet Assay in Evaluating DNA Damage Associated With Ischaemia-Reperfusion Injury in Patients Undergoing Coronary Surgery

Ischaemia-reperfusion (I/R) injury is responsible for a number of conditions such as coronary bypass and myocardial infarction, and deaths. Oxygen-free radicals formed during I/R have been proposed as the leading causes of tissue injury, and they play an important role in I/R injury. I/R induces oxidative DNA damage (such as purinic and pyrimidinic base lesions). Comet assay is a suitable and sensitive method for early detection of low-level DNA damage. We used modified alkaline comet assay in peripheral blood lymphocytes and evaluated I/R-induced DNA damage in patients undergoing coronary artery bypass graft (CABG) operation (in vivo model for I/R). No statistically significant difference in DNA damage levels was found before surgery, after anaesthesia, ischemia, reperfusion, and surgery. However, blood lactate levels (assessed in parallel with the comet assay) increased after I/R and did not return to the baseline level. Our findings showed that I/R injury did not induce DNA damage, but increased the lactate levels. This finding suggests that there might be reversible and uncommon necrosis that did not reflect on overall DNA base damage. Further studies are needed using this approach.