Browsing by Subject "Aflatoxin"
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Item Open Access Acquired tolerance of hepatocellular carcinoma cells to selenium deficiency: a selective survival mechanism?(American Association for Cancer Research, 2003) Irmak, M. B.; Ince, G.; Ozturk, M.; Cetin Atalay, R.Selenium is essential to human health, and its deficiency is associated with different diseases including liver necrosis. Selenium is protective against viral hepatitis and hepatocellular carcinoma (HCC). The underlying molecular mechanisms of selenium effects are not well known. In this study, in vitro response of HCC-derived cell lines to selenium deficiency is examined alone or in conjunction with Vitamin E and copper/zinc. Here, we show that itt vitro selenium deficiency in a subset of HCC-derived cell lines causes oxidative stress and cytochrome c release with subsequent cell death by apoptosis. The oxidative stress and consequent cell death induced by selenium deficiency on these cells are reverted by the antioxidant effect of Vitamin E. However, most HCC cell lines (10 of 13) tolerate selenium deficiency. Consequently, they escape apoptosis. Moreover, nine of these tolerant cell lines have integrated hepatitis B Virus (HBV) DNA in their genomes, and some display p53-249 mutation, indicating past exposure to HBV or aflatoxins, established factors for oxidative stress and cancer risk in liver. An HBV-transfected clone (2.2.15) of the sensitive HepG2 cell line has gained tolerance to selenium deficiency. Our findings indicate that selenium deficiency induces apoptosis in some "hepatocyte-like" cells. However, most HCC cells, particularly HBV-related ones, tolerate selenium deficiency and escape its deadly consequences. Thus, as demonstrated by the gain of survival capacity of apoptosis-sensitive cell lines with Vitamin E, such malignant cells have acquired a selective survival advantage that is prominent under selenium-deficient and oxidative-stress conditions.Item Open Access Aflatoxin genotoxicity is associated with a defective DNA damage response bypassing p53 activation(John Wiley & Sons, 2011) Gürsoy-Yüzügüllü, Özge; Yüzügüllü, Haluk; Yılmaz, Mustafa; Öztürk, MehmetBackground: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths. Aflatoxins, which may play a causative role in 5-28% of HCCs worldwide, are activated in liver cells and induce principally G→T mutations, including the TP53 codon 249(G→T) hotspot mutation. The DNA damage checkpoint response acts as an antitumour mechanism against genotoxic agents, but its role in aflatoxin-induced DNA damage is unknown. Aim: We studied the DNA damage checkpoint response of human cells to aflatoxin B1 (AFB1). Methods and results: The treatment of HepG2 hepatoma cells with mutation-inducing doses (3-5μmol/l) of AFB1 induced DNA adducts, 8-hydroxyguanine lesions and DNA strand breaks that lasted several days. Persistent phospho-H2AX and 53BP1 foci were also detected, but cell growth was not affected. AFB1-exposed HepG2 cells formed phospho-H2AX and 53BP1 foci, but failed to phosphorylate both Chk1 and Chk2. Huh7 hepatoma and HCT116 colorectal cancer cell lines also exhibited a similarly incomplete checkpoint response. p53 phosphorylation also failed, and AFB1-exposed cells did not show p53-dependent G1 arrest or a sustained G2/M arrest. These observations contrasted sharply with the fully functional DNA damage response of cells to Adriamycin. Cotreatment of cells with AFB1 did not inhibit p53 and p21Cip1 accumulation induced by Adriamycin. Thus, the deficient checkpoint response to AFB1 was not due to an inhibitory effect, but could be explained by an inefficient activation. Conclusion: Genotoxic doses of AFB1 induce an incomplete and inefficient checkpoint response in human cells. This defective response may contribute to the mutagenic and carcinogenic potencies of aflatoxins.Item Open Access Classification of agricultural kernels using impact acoustic signal processing(Bilkent University, 2006) Onaran, İbrahimThe quality is the main factor that directly affects the price for many agricultural produces. The quality depends on different properties of the produce. Most important property is associated with health of consumers. Other properties mostly depend on the type of concerned vegetable. For instance, emptiness is important for hazelnuts while openness is crucial for the pistachio nuts. Therefore, the agricultural produces should be separated according to their quality to maintain the consumers health and increase the price of the produce in international trades. Current approaches are mostly based on invasive chemical analysis of some selected food items or sorting food items according to their color. Although chemical analysis gives the most accurate results, it is impossible to analyze large quantities of food items. The impact sound signal processing can be used to classify these produces according to their quality. These methods are inexpensive, noninvasive and most of all they can be applied in real-time to process large amount of food. Several signal processing methods for extracting impact sound features are proposed to classify the produces according to their quality. These methods are including time and frequency domain methods. Several time and frequency domain methods including Weibull parameters, maximum points and variances in time windows, DFT (Discrete Fourier Transform) coefficients around the maximum spectral points etc. are used to extract the features from the impact sound. In this study, we used hazelnut and wheat kernel impact sounds. The success rate over 90% is achieved for all types produces.Item Open Access Detection of underdeveloped hazelnuts from fully developed nuts by impact acoustics(American Society of Agricultural and Biological Engineers, 2006) Onaran, I.; Pearson, T. C.; Yardimci, Y.; Çetin, A. EnisShell-to-kernel weight ratio is a vital measurement of quality in hazelnuts as it helps to identify nuts that have underdeveloped kernels. Nuts containing underdeveloped kernels may contain mycotoxin-producing molds, which are linked to cancer and are heavily regulated in international trade. A prototype system was set up to detect underdeveloped hazelnuts by dropping them onto a steel plate and recording the acoustic signal that was generated when a kernel hit the plate. A feature vector comprising line spectral frequencies and time-domain maxima that describes both the time and frequency nature of the impact sound was extracted from each sound signal and used to classify each nut by a support-vector machine. Experimental studies demonstrated accuracies as high as 97% in classifying hazelnuts with underdeveloped kernels.Item Open Access Genetic aspects of hepatocellular carcinogenesis(1999) Ozturk, M.Hepatocellular carcinoma (HCC) is linked etiologically to viruses (hepatitis B virus [HBV] and hepatitis C virus [HCV]), chemical carcinogens (i.e., aflatoxins), and other environmental and host factors causing chronic liver injury. Some hepatoblastomas may be linked to inherited gene mutations, but adult hereditary HCC appears to be rare. HCCs display gross genomic alterations, including DNA rearrangements associated with HBV DNA integration, loss of heterozygosity, and, less importantly, chromosomal amplifications and loss of imprinting. Many genes with somatic mutations have now been identified in these tumors. Most frequently involved genes are tumor suppressor genes such as p53, M6P/IGF2R, β-catenin, p16INK4A, and retinoblastoma genes. Most identified mutations are somatic, but germline mutations of p16INK4A, APC, and BRCA2 have also been reported. Oncogenic activation of several cellular genes such as cyclin D and cyclin A have been described in HCC, but the possible implication of candidate viral oncogenes (i.e., X protein of HBV) is still debated. A comprehensive analysis of all the genetic changes described for HCC demonstrates that at least four different growth regulatory pathways are altered in these tumors. However, each pathway appears to be implicated in a limited fraction of these tumors, suggesting that HCCs are genetically heterogenous neoplasms. This genetic heterogeneity correlates with the heterogeneity of etiologic factors implicated in HCC.Item Open Access Signal and image processing algorithms for agricultural applications(Bilkent University, 2006) Dülek, BerkanMedical studies indicate that acrylamide causes cancer in animals and certain doses of acrylamide are toxic to the nervous system of both animals and humans. Acrylamide is produced in carbohydrate foods prepared at high temperatures such as fried potatoes. For this reason, it is crucial for human health to quantitatively measure the amount of acrylamide formed as a result of prolonged cooking at high temperatures. In this thesis, a correlation is demonstrated between measured acrylamide concentrations and NABY (Normalized Area of Brownish Yellow regions) values estimated from surface color properties of fried potato images using a modified form of the k-means algorithm. Same method is used to estimate acrylamide levels of roasted coffee beans. The proposed method seems to be a promising approach for the estimation of acrylamide levels and can find applications in industrial systems. The quality and price of hazelnuts are mainly determined by the ratio of shell weight to kernel weight. Due to a number of physiological and physical disorders, hazelnuts may grow without fully developed kernels. We previously proposed a prototype system which detects empty hazelnuts by dropping them onto a steel plate and processing the acoustic signal generated when kernels hit the plate. In that study, feature vectors describing time and frequency nature of the impact sound were extracted from the acoustic signal and classified using Support Vector Machines. In the second part of this thesis, a feature domain post-processing method based on vector median/mean filtering is shown to further increase these classification results.