The Influence of Oxidative Stress, Carcinogens and Cloning on DNA ...

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Introduction DNA methylation Gene hypermethylation Global genomic hypomethylation Figure 5: <strong>The</strong> effect <strong>of</strong> methylation level in tumour cells On the other h<strong>and</strong>, the overall genomic hypomethylation was associated with few human ma- lignancies such as colonic neoplasias (100, 101) , lung carcinoma (102) <strong>and</strong> metastatic prostate carcinoma (103) . DNA hypomethylation, however, was detected as an important spot in breast carcinoma (88) . Global hypomethylation affects DNA in repetitive sequences as well as centromeres * resulting in chromosome instability, loss <strong>of</strong> imprinting <strong>and</strong> increased mutation rate. A reduction in the genomic content <strong>of</strong> 5-meC varied from 8% to 31% according to carcinogen type was determined in other specific studies concerning bronchial epithelial cells treated with a broad range <strong>of</strong> chemical carcinogens (104) . Medical researches illustrated that hypomethylation is present at early stages <strong>of</strong> chronic lymphocytic leukaemia (B-CLL) (105) . In conclusion, DNA methylation can be used as biomarker for diagnosis <strong>of</strong> cancer because the pr<strong>of</strong>iles <strong>of</strong> DNA alterations characterizing a certain cancer type were helpful as cancer diagnostics, moreover the inactivated genes by promoter region hypermethylation provide a fundamental link <strong>of</strong> these inactivation patterns corresponding to specific tumours (106) . Importantly, the altered DNA methylation-caused tumour is a reversible epigenetic mutation <strong>of</strong>fering targets for therapeutic drugs. DNA-methyltransferase inhibitor drugs as 5'-azacytidine, decitabine <strong>and</strong> histone deacetylase inhibitors are being used as chemotherapeutic agents to treat some kinds <strong>of</strong> tumours (1, 107) . 5-methylcytosine 10 Inactivation <strong>of</strong> DNA repair Defect <strong>of</strong> signal transmission between cells Loss <strong>of</strong> apoptosis Mutation <strong>of</strong> 5-medCMP to thymine Chromosome instability Increase mutation rate Loss <strong>of</strong> imprinting
1.2.6 In-vitro fertilization (IVF) 11 Introduction Several assisted reproduction technologies (ART) were established to solve the infertility problems (108) . In vitro-fertilisation (IVF), one <strong>of</strong> the most significant ART had shown success to conceive baby in 1976 then the development <strong>of</strong> its exp<strong>and</strong>ed techniques, most importantly to be cited the intracytoplasmic sperm injection (ICSI) (109) , had really helped the infertile couples to conceive infants. However, different birth defects (110, 111) had been remarked in some cases like chromosomal abnormalities, cardiovascular defects, growth abnormalities (112, 113) as well as high risk <strong>of</strong> low birth weight. Hansen et al (114) had declared that the babies con- cieved by IVF have twice the rate to develop major birth defects as compared to naturally conceived children. Additionally, IVF was reported to be associated with diseases like An- gelman syndrome (AS) (115) <strong>and</strong> Beckwith-Wiedemann syndrome (BWS) (116, 117) that etiologically related to aberrant genomic imprinting (118, 119) . <strong>The</strong> epigenetic modifications <strong>of</strong> the genome including DNA methylation <strong>and</strong> histone modification are linked through their functions <strong>and</strong> synchronously affecting each other. DNA methylation as an important factor in modeling the structural patterns <strong>of</strong> genome was investigated in IVF in different studies. Different methylation status was reported (120, 121) depending on the protocol <strong>of</strong> in vitro embryo formation as well as tissue specificity (120) . IVF could affect the DNA methylation via imprinting errors that happened during this in vitro reproduction technique (122, 123) . 1.2.7 <strong>Cloning</strong> Somatic cell nuclear transfer (SCNT), or cloning, is a technique used to create genetically identical animals by somatic cell nuclear transfer into unfertilized eggs. In this technique, the nuclear genetic material is transferred from the animal that should be cloned (known as genetic donor) into a recipient cell matured oocyte or unfertilised egg (cytoplast) from which the genetic material has been removed. <strong>The</strong>n, the somatic cell taken from genetic donor is inserted into the enucleated egg <strong>and</strong> the fusion <strong>of</strong> two cells is accomplished by electricity. <strong>The</strong> fused egg is activated for the reproduction. <strong>The</strong>n the activated egg is placed in a culture medium. <strong>The</strong> cellular division is watched till an early-stage embryo (blastocyst) is formed <strong>and</strong> then is transferred to a recipient female (sometimes referred to as ’surrogate mother’) for the subsequent development (124) .
Page 1 and 2: The Influe
Page 3 and 4: The work at h<stro
Page 5 and 6: First, I feel always grateful to Al
Page 7: I would like to extend my thanks to
Page 11 and 12: The following acro
Page 13 and 14: FDA Food and drug
Page 15: RIA Radioimmunoassay ROS Reactive o
Page 18 and 19: Index 3.1 Spectrophotometeric deter
Page 20 and 21: Index 5.2.4.2 Dialysis of</
Page 22 and 23: Introduction 1.1.2 DNA methylation
Page 24 and 25: Introduction 1.2 The</stron
Page 26 and 27: Introduction Figure 4: Model for me
Page 28 and 29: Introduction Cancer is classified i
Page 32 and 33: Introduction 1.2.7.1 Clonin
Page 34 and 35: Introduction 1.2.8 Twins an
Page 36 and 37: Introduction chemicals, alkylating
Page 38 and 39: Introduction AP sites are not only
Page 40 and 41: Introduction 1.3.2.1 Oxidat
Page 42 and 43: Introduction Finally, flavo- <stron
Page 44 and 45: Introduction chromatography with el
Page 46 and 47: Introduction One of</strong
Page 48 and 49: Introduction facturing of</
Page 50 and 51: Introduction 320) ; but due to its
Page 52 and 53: Introduction HO O O Figure 15: Mech
Page 54 and 55: Introduction - Methylation Sensitiv
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Page 58 and 59: Introduction - Radioactive-mediated
Page 60 and 61: Aim and objectives
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Results and Discus
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Summary 4 Summary DNA methylation i
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Summary The same s
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Experimental part Sodium tetrapheny
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Experimental part � Sodium tetrab
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Experimental part framework was fas
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Experimental part propanol
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Experimental part 12.5 mU/µL SPD)
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Experimental part Condition Value D
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Experimental part 5.4 Instrumentati
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Experimental part Graduated cylinde
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Experimental part 3-Nitrobenzanthro
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Appendix In-vitro: Denoting a react
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Appendix Laboratory Document Hydrol
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Appendix BODIPY and</strong
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Appendix Description of</st
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Appendix Transmission [%] 120 100 8
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Appendix Figure 62: Mass spectrum E
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List of figures Fi
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List of tables 8 L
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Literature Literature 1. Egger, G.;
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Literature 41. Bestor, T.H.; "<stro
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Literature 78. Venitt, S.; "Mechani
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Literature 113. Sinclair, K.D.; Mce
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Literature 148. Kadan-Lottick, N.S.
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Literature cyte DNA by gas chromato
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Literature 221. Mirand</str
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Literature 257. Lingaraju, G.M.; Sa
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Literature different tissues <stron
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Literature 324. Vishwanath, B.S.; F
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Literature 359. Wei, L.; Li, R.K.;
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Literature 394. Ramsahoye, B.H.; "M
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Literature 431. Wirtz, M.; Schumann
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Literature 467. Cornelius, M.; Wort
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Literature 502. Issa, J.P.J.; Ottav
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Literature 536. Pinheiro, J. <stron
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