5-Azacytidine is a Potential Chemotherapeutic Agents for Cancer

Epigenetics refers to external modifications to DNA that turn genes on or off. These alterations do not change the DNA sequence, but instead, they affect how cells read genes. One common example of an epigenetic change is DNA methylation. DNA methylation is the addition of a methyl group to part of the DNA molecule which prevents certain genes from being expressed. It should be noted that epigenetics is a fairly new subdivision in genetics and its importance in evolution and heritability is currently being developed and debated (Furrow 2011).

Then after DNA was extracted from a mouse live, and brain, the DNA decreased as it age ((DiMauro & David, 2009). DNA methylation is a procedure by which methyl gatherings are added to DNA. Once it is added, DNA’s function changes. Then if it is located in the promoter, the represses transcription, and transcription is important to constructing a gene expression. Early studies were on certain organs and life cycle of a humpback salmon. The studies on the salmon showed the 5-methylcytosine and otogenesis were decreasing. This shows the relationship between methylation and growth. Xist, H19,TARID are just a few noncoding RNA that affects methylation (Grammatikakis, Panda, Abdelmohsen, & Gorospe, 2014) . Xist is a RNA gene that is found on the X chromosome in mammals specifically females to level out the dosage effect in males. H19 is another lnRNA that limits body weight and cell production, but plays apart in the embryonic development and growth. Its controls imprinting and the loss of imprinting increases age related diseases. TARID prompts demethylation, and this helps trigger tumor suppressor

When chemical tags are labeled the modifications are called epigenetic modification. These can be classified as modifications that take place on or above the genes. Epigenetic modification permits lasting changes in gene expression. Epigenetics studies the changes in gene expression or development caused by mechanisms other than changes in the primary DNA sequence. Epigenetics demonstrates how DNA interacts with the multitude of smaller molecules found within cells which can activate and deactivate cells. Epigenetics can be highly based off of nature versus nurture. Epigenetic changes are a part of normal development. As genes are activated some are

While the mice in the experiments had no gene modifications/mutations, genes were turned off/on when environmental factors were altered, creating a variety of unexpected traits in the offspring of mice (Moalem 159-160). These factors are hard to account for and are good examples of how genetic information varies greatly and is not perfect. Understanding of genetic variation and methylation is difficult and is a complex topic being

The impact that this has for our understanding of tumour formation, and the potential clinical implications, confirms my interest in it. To explore this further, I read “The Epigenetics Revolution” by Nessa Carey, where I found the actual mechanisms of epigenetic modification compelling, especially the role of histone modification in promoting the longer-lived DNA methylation. The vital role of gene regulation in our biology intrigues me, as it increases the complexity of how genotype translates to

Genomic imprinting does not follow the standard Mendelian rules of inheritance. Instead the single allele from a specific parent is preferably expressed over the other allele even if both are normal, functional versions (“Genetic Analysis”). The amount of methylation on the cytosine nucleotides of a sequence called the imprinting control region (ICR) governs the imprinted genes. In general increased methylation decreases expression of the gene and vice versa.

Chromatin changes have been linked with all phases of tumour creation and development. The best categorized are epigenetically mediated transcriptional-silencing activities that are related by increases in DNA methylation, specifically at promoter regions of genes that control important cell functions. Current proof shows that epigenetic changes would possibly 'addict' cancer cells to alter signal-transduction pathways in the early stages of tumors development. Reliance on these pathways for cell proliferation or existence allows them to obtain genetic mutations in the same pathways, providing the cell with careful advantage that promote tumors progression. Approaches to inverse epigenetic gene silencing might consequently be beneficial in cancer prevention and treatment [75].

In this experiment it was shown that the DNA methylation is inversely correlated with the expression of the genes, IAPV. The longer the stain the less methylated it was. It also shows the honey bee response is different from human response that had been studied.

Cancer is the uncontrolled division and growth of cells within the body. (Appendix 1) These cells are usually abnormal and are caused by mutations in genes that control the cell growth and replication. These cells damage the normal function of organs and can form tumours. Anti-cancer drugs work using number of strategies that interferes with the mitosis of the body cells, which in turn slows down the growth of the cancerous tissues. Anticancer drugs have distinct mechanisms of action which may vary in their effects on different types of cancer cells. These mechanisms of action are divided into three main categories. Anticancer drugs generally do one of the following, stop the synthesis of the pre-cursors of the DNA synthesis, damage the nucleic acid of the cell or affect the formation of the mitotic spindle. This is displayed in appendix 2. All three interfere with the division of the cells, which in turn slows down the growth of the cancerous tissue.

The activity of genes is reliant on mostly on whether they are available to transcription factors; this is vastly controlled by the dynamics of chromatin restructuring. Epigenetic modifications on the chromatin play a vital role in regulating the construction of chromatin and thus the availability of DNA for transcription. Some of the sites at the DNA that are transcripted can be turned on or off by epigenetic changes. Moreover, it has previously been verified that environmental factors, for example diet, cigarette and alcohol use, stress, or exposure to chemical carcinogens and infectious agents, Sexuality and age effect the epigenome. Today, because of importance in epigenetic processes, most scientists prefer to work in this field of research.

Human development from conception to adulthood is a conjoined partnership, moulded within our cells, of Nature (the DNA we inherit) and Nurture (the prevailing nutritional, social and physical environment). The field of epigenetic is quickly growing and with it the understanding that both the environment and individual lifestyle can also directly interact with the genome to influence epigenetic change. Developing organisms seem to have a wide range of susceptibility to epigenetic changes. Appropriate dynamics in epigenetic modifications are essential for embryogenesis, early fetal development and early postnatal growth. Consequently, the inadequate establishment of epigenetic modifications during critical developmental periods due to changes

Since Gregor Mendel’s discovery of alleles and genetic inheritance, there has been research shows that there are more mechanisms of inheriting traits which do not include changing the nucleotide sequence of DNA. This form of non-genetic inheritance is called epigenetic modification. One example of epigenetic modification is DNA methylation. DNA methylation is when methyl groups, which are chemical groups that contain one carbon bound to three hydrogen atoms,

Current pharmaceutical companies have developed many compounds for cancer treatment that lack the identification of cellular targets, leading to the absence of cell type specificity in treatment. However, series of compounds hereafter referred to as de Lijser compounds, have been

Epigenetics can be hereditable or environmental factors that affect the expression of genes and lead to changes in gene expression. Unlike genetics, epigenetics does not only have to do with which genes are passed down to the offspring and the DNA sequence. The environmental conditions of the offspring’s parents impact the genes in their eggs and sperms by “switching on” certain genes and “switching of” others (Dowshen). Since the genes expression of the gametes are affect, the phenotypes of the offspring will change. Even in a person’s lifetime, environmental factors such as stress, chemical exposure, and diet can continue to impact gene expression through DNA methylation. During DNA methylation, a methyl group is randomly added to a 5-carbon cytosine ring, making 5-methylcytosine and these groups inhibit transcription. (Cheriyedath). Due the fact that transcription is not possible, the expressing of the genes in that section of the DNA strand will be suppressed. The attachment of the methyl group to DNA is not determined, which means that

Another importance of DNA methylation is production of chromatin structure, which leads to growth of a single cell in an uncontrolled level to a complex multicellular organism. It also causes the development of cancer. According to new studies, the genes with a promoter region which has higher ratio of methylated cytosine are transcriptionally silent. Aberrant DNA methylation increases the rate of malignancy. Mainly there are two types of methylation: hyper methylation which control the activation of genes, and hypo methylation leads to the development of cancer through various processes.