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العنوان
Applications of DNA Microarrays in Toxicology\
المؤلف
Younis, Ahmad Fadl Allah.
هيئة الاعداد
باحث / Ahmad Fadl Allah Younis
مشرف / Hani Ahmed Gamaluddin
مشرف / Khadija Abdul Fattah Mustafa
مناقش / Nesrine Mohamed Sarhan
تاريخ النشر
2014.
عدد الصفحات
207p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب (متفرقات)
تاريخ الإجازة
1/1/2014
مكان الإجازة
جامعة عين شمس - كلية الطب - علم السموم
الفهرس
Only 14 pages are availabe for public view

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Abstract

Summary and Conclusion
DNA microarray is a powerful tool that uses genome sequence
information to analyze the structure and function of tens of thousands
of genes at a time.
A microarray is typically defined as a collection of microscopic
spots arranged in an array or grid-like format and attached to a solid
surface or membrane. These spots typically referred to as probes, are
designed such that each probe binds a specific nucleic acid sequence
corresponding to a particular gene through a process termed
hybridization. The sequence bound to a probe, often referred to as the
target, is labelled with some kind of detectable molecule such as a
fluorophore. The level of binding between a probe and its target is
quantified by measuring the fluorescence or signal emitted by the
labelling dye when scanned. This signal provides a measure of the
expression of the specific gene containing the target sequence.
There are two main DNA microarray technological platforms,
spotted arrays and in-situ oligonucleotide arrays, each has unique
characteristics.
Each Microarray experiment typically follows several steps in
defined order, array fabrication, target preparation, hybridization,
signal detection and visualization, and data processing and analysis.
DNA microarray-based techniques have been applied in
identification of biomarkers, screening of single nucleotide
polymorphisms, detection of pathogens and factors related to their
virulence and drug resistance, detection of chromosomal
abnormalities, detection of monogenic disease-related mutation,
identifying genes linked to multi-step development process of cancer
and genes related to drug abuse, in forensic chemistry and in food
sciences. In many cases, they allowed accurate and rapid results.
Also, Microarrays are becoming routine procedures in
pharmaceutical companies replacing many conventional techniques.
Microarrays have been found to provide useful information in the
different stages of the drug discovery process.
The potential of DNA microarray technology to identify gene
expression changes associated with toxic or pharmacologic processes
has been the focus of several studies.
Acetaminophen, arsenic, clofibrate, methapyrilene and carbon
tetrachloride are known to be hepatotoxic. DNA microarrays had been
used to identify gene expression profiles of those hepatotoxicants
leading to a better understanding of the molecular basis of their
hapatotoxicity.
Also, Microarrays were used for identification of candidate
molecular markers of kidney toxicity. Also, the mechanisms of
ochratoxin that is known to cause severe nephrotoxicity in animals
and humans, marked changes were detected for genes involved in
DNA damage response and apoptosis, response to oxidative stress,
and inflammatory reactions.
Neurotoxins such as lead, dopamine, dieldrin,
methylazoxymethanol and nitrogen mustard are widely used
substances. However, the molecular mechanisms underlying their
neurotoxicity are not fully characterized. DNA microarrays had been
used to identify altered gene expression following these neurotoxins to
identify potential mechanisms of their neurotoxicity.Cardiotoxicity is a serious adverse effect of many drugs and toxins.
DNA microarrays studies revealed down regulation of many genes
reflecting the underlying mechanisms of drug induced cardiotoxicity.
Ozone is an oxidant gas that can directly induce lung injury. DNA
microarrays has been used to develop biomarkers to its exposure or
response.
DNA microarrays studies are beneficial in studying
hematotoxicity, skin toxicity, reproductive toxicity, immunotoxicity
and toxic effects of many environmental toxicants.
The DNA microarrays studies done have showed differential genes
expressions in response to various agents and their effects on multiple
organs providing the mechanistic response of cellular derangement
that occurred on exposure to those agents. This helps in providing new
predictive biomarkers for subsequent clinical use that can be used as
early indicators of toxicity and aid in improving of diagnostic assays
as well as provision of new therapies.
DNA microarrays analysis data can be combined with data from
other omics approaches in an attempt to investigate mechanistic
pathways in more details that will have a major impact on the field of
toxicology.
However, Microarrays continue to have limitations in addition to
their technical difficulty since the large data sets generated by the
chips add new statistical and informatics-related challenges and
complexity. There are also several experimental design issues that
could impact the analysis.