Breast cancer is the most frequent malignancy among women, especially in Western societies. Highly penetrant genes such as BRCA1 and BRCA2, together with the reproductive history can constitute only 30% of the cause, so there should be other common genes, which may play a role in breast carcinogenesis according to one&#039 / s lifestyle. In our case, the effect of N-acetyl transferases (NAT1, NAT2) and glutathione-S transferases (GSTM1&amp / GSTT1) were investigated, since variations in these genes may alter their enzymatic activity and therefore their capacity to biotransform xenobiotic compounds. To evaluate the potential association between NAT1, NAT2, GSTM1 and GSTT1 genotypes and development of breast cancer, a hospital based case-control study was conducted in a Turkish study population consisting of 37 histologically confirmed incident breast cancer cases and 34 control subjects with no present or previous history of cancer. The only recognizable difference between case and control groups is the percentage of GSTM1 deletion, 67.6% and 44.1% respectively (p=0.047). The frequency of rapid NAT2 acetylator genotype is 44.4% in cases and 23.5% in controls. Especially, women with NAT2 rapid acetylator and GSTM1 null genotypes were at the elevated risk (OR, 3.8 / CI, 0.9-15.4). NAT1 rapid acetylator genotype showed no association with breast cancer. These results suggest that GSTM1 null genotype is a susceptibility factor for breast cancer, particularly in the presence of NAT2 rapid acetylator genotype.

Stroke is an important public health problem and the third leading cause of death after coronary heart diesase and all cancers in all over the world. Free radicals and oxidative stress play important role in the pathogenesis of several diseases including atherosclerosis, stroke, cancer, neurodegenerative diseases such as Alzheimer&#039 / s dementia. The activity of paraoxonase (PON1) aganist phenylacetate is known as arylesterase (ARE). Paraoxonase is an esterase associated with high-density lipoprotein (HDL) and contributes to the protective role of this lipoprotein on low-density lipoprotein (LDL) oxidation. Oxidized LDL is known to play a central role in early events in the progression of atherosclerosis which is a risk factor for stroke. Glutathione S-transferases (GSTs) catalyze the conjugation of nonpolar compounds to reduced glutathione (GSH) and detoxify toxic metabolites produced within the cell by oxidative stress to protect cells from oxidant injury. v The maximum ARE enzyme activity was detected at 10 mM Tris-HCl buffer, pH 8.0 and at 45 &deg / C. ARE enzyme was saturated with its substrate phenylacetate around 20 mM concentration. The apparent Km and Vmax values of human blood serum ARE for phenylacetate were found as 1.66 mM and 3300 nmol/min/mg, respectively. The maximum GST enzyme activity was detected at 2 mM potassium phosphate buffer, pH 5.5 and at 65 &deg / C. GST enzyme was saturated with its substrate, CDNB around 4.5 mM concentration and with its cofactor, GSH around 8 mM concentration. The apparent Km and Vmax values of human blood serum GST for CDNB substrate were found as 2.8 mM and 0.43 nmol/min/mg and for GSH were found as 4.11 mM and 0.23 nmol/min/mg, respectively. In addition, effects of three different heavy metal ions, Cd+2, Hg+2 and Ni+2, on human blood serum ARE and GST activity were studied and half maximal inhibitory concentrations (IC50) were determined. The main objective of this study was to investigate the human blood serum ARE and GST activities in patient and control groups using the optimized conditions. For this purpose, blood samples were collected from 172 ischemic stroke patients and 105 controls. Then serum obtained from blood samples were used to determine ARE and GST activities. The mean of ARE activity in patient group (n=172, 109.9 &plusmn / 32.5 U/mL ) was insignificantly lower than the mean of ARE activity in control group (n=105, 113.5 &plusmn / 33.1 U/mL, P=0.284). GST activity of the patients (10.8 &plusmn / 4.4 U/L) was insignificantly higher than that of controls (10.5 &plusmn / 4.2 U/L, P=0.483 ). In addition, statistical analysis showed hypertension, diabetes and HDL as significant risk factors of stroke.

Prostate cancer (PCa) is one of the most prevelant cancers in males in many countries, increasing in frequency with age. PCa incidence and mortality rates are not evenly distributed worldwide. Family history is an established risk factor for prostate cancer and families demonstrating autosomal dominant or X-linked transmission of susceptibility have been observed. Although an increasing number of candidate genes or hereditary prostate cancer susceptibility have been identified, only 5 to 10 percent of prostate cancer cases in the population may arise from major susceptibility genes. A few risk factors for PCa development are advanced age, an intact androgen metabolism, ethnicity, and genetic background. Other genetic factors, in combination with possible environmental risk factors for prostate cancer, may have greater public health importance. Genetic polymorphisms that may be associated with prostate cancer risk are much more common in the population than are high-penetrance cancer susceptibility genes. In this study, the effect of N-acetyltransferase 2 (NAT2) and Glutathione S-transferases (GSTM1 and GSTT1) were investigated, since polymorphism in these genes may alter their enzymatic activity and, therefore, their capacity to biotransform xenobiotic compounds. In order to evaluate the potential association between NAT2 , GSTM1 and GSTT1 genotypes and prostate cancer risk, a hospital based case control study was carried out in a Turkish population consisting of 30 histologically confirmed incident prostate cancer cases and 67 control subjects with no present or previous history of cancer. The GSTM1 and GSTT1 genotypes showed no significant differences between case and control groups, with respect to their frequencies and it was observed that GSTM1 null genotype was more common in cases with a 60% frequency. Even though the frequency of slow NAT2 acetylator genotype was 80% in cases and 50,7% in controls NAT2 rapid acetylator showed no association with prostate cancer statistically. These results suggested that GSTM1 null genotype is a susceptibility factor for prostate cancer, particularly in the presence of NAT2 slow acetylator genotype with no significance. Further studies with a larger size are required to confirm the presence and significance of this relationship.

Free radicals which have critical roles in living systems through their beneficial and detrimental effects play an important role in medical revolution in health. Radicals are produced in the cells and tissues of our bodies by various processes and reactions. Diabetes mellitus is an extremely common disease in the world which seems to be accompanied by a shortage of antioxidants and an increase in free radicals, the end result of oxidative stress. Glutathione S-Transferases (GST / EC 2.5.1.18) are found in enzymatic defense system which has a role in defending cells against potentially toxic and/or carcinogenic compounds. In this study, the changes in the activities and expressions of various GST isozymes in the liver of diabetic rats related to oxidative stress were studied. The effects of antioxidants, Vitamin C and &amp / #945 / -Lipoic acid on GST isozyme activities and mRNA expressions were also investigated. According to our results, diabetic rats exhibited decreased mRNA expressions of both GSTA2 and GSTM1 genes, but the activities of only GST Mu isozyme decreased in diabetic rats, compared to controls and GST Alpha isozyme activity remained unchanged in diabetic animals. Our results also showed that &amp / #945 / -Lipoic acid individually has no significant effect on both GSTA2 and GSTM1 gene expressions and activities. Furthermore, although the administration of Vitamin C alone showed no significant effect on all GST isozyme activities, it decreased GSTA2 mRNA expression significantly. The administration of Vitamin C and &amp / #945 / -Lipoic acid together affected both GSTA2 and GSTM1 mRNA expressions in control rats, but only GST Mu activity showed a significant change. The results of this study showed that, the administration of two antioxidants, &amp / #945 / -Lipoic acid and Vitamin C alone and together did not reverse the results of diabetes at the level of both gene expression and activities of GST isozymes.

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a phytoestrogenic component of Rheum plant extracts which has been used for medical treatment since ancient times. It has been shown to have anti-inflammatory and anti-cancer effects. In our research, we aimed to study the biological effects of emodin on MCF-7 and MDA-231 cell lines. Cytotoxicity assays showed that emodin treatment for 48hours caused a concentration dependent decrease in viable cell numbers of both cell lines. As determined by cell counting with tryphan blue, IC50 values were 8.40 and 12.17 &micro / g/ml for MCF-7 and MDA-231 cells, respectively. Apoptotic effects of emodin was investigated by measuring the changes in apoptotic and antiapoptotic gene expressions by qRT-PCR. In MCF-7 cells, Bax expression increased with increasing emodin concentrations, while Bcl-2 expression was downregulated. Bax/Bcl-2 ratio was calculated as 9.2 fold at 10&micro / g emodin/ml treatment for 48 hours, indicating stimulation of apoptosis. However, Bax/Bcl-2 ratio was found 1.6 fold for MDA-231 cells. These results were in accordance with the results obtained from microarray analysis of related gene expressions. MCF-7 cells were more apoptotic in comparison to MDA-231 cells. DNA fragmentation was observed in MCF-7 cells by TUNEL method. GST enzyme activity that was measured using CDNB as substrate, was increased 100% with respect to control up to 5&micro / g emodin/ml treatment of MCF-7 cells for 48 hours. However, effect of emodin on GST activity in MDA-231 cells was found insignificant. According to microarray analysis results, emodin affected the gene expressions of GST isozymes in MCF-7 cells much more than in MDA-231 cells.

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Thesis (Ph. D.)--University of Missouri-Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves 141-152). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 156-168). Also available on the Internet.

Reproduction de : Thèse doctorat : Pharmacie. Biochimie et biologie moléculaire : Reims : 2004. / Bibliogr.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 156-168). Also available on the Internet.