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العنوان
Applications of Biomarkers in Toxicology – A Comprehensive Review /
المؤلف
Hassan, Azza Omar.
هيئة الاعداد
باحث / عزه عمر حسن محمود
مشرف / سهير علي محمد
مشرف / ولاء احمد السيد علام
مشرف / مها عبدالحميد هلال
مشرف / مني القطب موسي
الموضوع
Biochemical markers. Toxicology.
تاريخ النشر
2017.
عدد الصفحات
194 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
علم الأمراض والطب الشرعي
تاريخ الإجازة
29/3/2017
مكان الإجازة
جامعة سوهاج - كلية الطب - الطب الشرعي والسموم الاكلينيكيه
الفهرس
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Abstract

The term “biomarker” a portmanteau of “biological marker”, refers to a
broad subcategory of medical signs that is objective indications of
medical state observed from outside the patient which can be measured
accurately and reproducibly. National Institutes of Health (NIH) defined
a biomarker as a characteristic that is objectively measured and evaluated
as an indicator of normal biologic processes, pathogenic processes, or
pharmacologic responses to a therapeutic intervention. Any specific
molecular alteration of a cell on DNA, RNA, metabolite, or protein level
can be referred to as a molecular biomarker.
The ideal biomarker should be ethically acceptable, easily sampled
dependent on simple chemical analysis, reflect a reversible change,
relevant, valid, specific and sensitive.
Toxicogenomics defined as the study of the relationship between the
structure and activity of the genome and the adverse biological effects of
exogenous agents. The term toxicogenomics encompasses
transcriptomics, metabonomics, and proteomics. It also defined as
studying of cell structure and function in response to toxic compound.
Pharmacogentic are studying the effect of genetic variation on the
individual in response to drug. Transcriptomics are studying alteration of
gene expression as a result of exposure to toxic compound .
Metabonomics are studying effect of toxic compound on cellular
metabolic effect. Proteomics are studying alteration in level of protein
expression in response to toxic compound.
Biomarkers have applications in all areas of toxicology, especially in
the field of pesticides, metals, and drugs. Measurement of residues of
pesticides and their metabolites, and metals in urine, serves as the most

accurate and reliable biomarkers of exposure in agriculture, industrial,
and occupational safety and health settings.
Biomarkers are playing an increasingly important role in drug
discovery and development from target identification and validation to
clinical application, thereby making the overall process a more rational
approach. The advantages of biomarkers are well recognized by the
research, medical and pharmaceutical communities. Biomarkers can
reduce time factors and costs for Phase I and II clinical trials by replacing
clinical endpoints. Biomarkers can also be helpful in redefining the
diseases and their therapies by shifting the emphasis of traditional
practices of depending on symptoms and morphology to a more rational
objective molecular basis.
Biomarkers of exposure allow the determination as to whether such
organisms have been exposed or not, because the presence of xenobiotics
or their metabolites in biological samples from the monitored individual
is undoubted proof of exposure. Thus, biomarkers of exposure are
suitable for assessing exposure to xenobiotics especially when the
organism is not in direct contact with the source of xenobiotics.
Biomarkers of effect are very important for in vivo and in vitro
toxicological testing as they are able to detect preclinical stages, they
offer molecular end-points to measure the response of the exposed system
to the assessed xenobiotics . Finally, biomarkers of susceptibility allow us
to identify, among all the people in a given population, those individuals
that are particularly susceptible to xenobiotics, which also would provide
better protection of these individuals.
Also computational toxicology is one of a growing research area that
is showing advances in molecular biology and chemistry with modeling

and computational science in order to increase the predictive power of the
field of toxicology. The U.S. Environmental Protection Agency (U.S.
EPA) defines computational toxicology as the ‘‘integration of modern
computing and information technology with molecular biology to
improve agency prioritization of data requirements and risk assessment of
chemicals.
Nowadays, temporal and spatial changes in selected biological systems
and parameters are used to reflect changes in environmental quality and
conditions. This biomonitoring approach can range from the assessment
of chemical residues in the tissues of living organisms, through to
assaying specific biological endpoints. The former, often involving the
use of biomarker, can be considered as one form of chemical-based
monitoring.
The latest technologies, such as microRNAs (miRNAs), have been
well recognized as reliable and robust biomarkers for early detection of
diseases, birth defects, pathological changes, cancer, and toxicities.
Because they are stable in biofluids, such as blood, there is rapidly
growing interest in using miRNAs as diagnostic, prognostic, and
predictive biomarkers, and the outlook for the clinical application of
miRNA discoveries is promising, especially in molecular medicine.
The application of miRNAs is still very new. Soon incorporating
pharmacological and toxicological targeting of miRNAs into the
development of innovative therapeutic strategies will be routine. Still,
more innovative biomarkers need to be developed that will be highly
sensitive (biotechnology-based techniques), require minimum quantities
of sample, and will promise high throughput screening.
Conclusion
In the field of toxicology, measurement of biomarkers reflects the
time-course of an injury and provides information on the molecular
mechanisms of toxicity. These biomarkers provide us the confidence of
accurate diagnosis, prognosis, and treatment. The biomarkers of early
chemical exposure can occur in concert with biomarkers of early disease
detection, and that information aids in avoiding further chemical exposure
and in strategic development of a novel treatment, including personalized
medicine (i.e. treating the patient, and not the disease). In essence, with
the utilization of specific biomarkers, an ounce of prevention can be
worth a pound of treatment.
In the toxicology field, biomarkers should be specific, accurate,
sensitive, valid, biologically or clinically relevant, and easy and fast to
perform in order to be useful as predictive tools for toxicity testing and
surveillance and for improving quantitative estimates of exposure and
dose. Therefore, biomarkers are utilized in biomonitoring data that are
useful in a variety of applications, from exposure assessment to risk
assessment and management.
Recommendation
 There is need for introducing more knowledge about
biomarkers in toxicology.
 More focusing on new biomarkers in toxicology.
 Introducing more and more technologies and instruments for
identifying a lot of biomarkers.
 Identify more about role of biomarkers for early diagnosis
of organ toxicity.
 There is need for more researches and data about miRNA to
be used accurately in toxicology.