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The DNA Damage and Toxicology Core provides
expertise, equipment and facilities to perform DNA damage and
toxicology studies related to toxic or hypoxic tissue/cell
injury in drug development, diseases or aging. In addition to
offering standard cytotoxicity assays, the core can measure
oxidative damage and quantify levels of apoptosis and necrosis
in cells and tissues by using quantitative cytochemistry,
immunocytochemistry techniques, and 3-D imaging.
Services Provided:
- Toxicity testing in vitro and in vivo
- Isolation of DNA in damage-free
conditions
- In vitro DNA fragmentation assays
- DNA fragmentation assays in cells
(single-cell DNA fragmentation through ds- or ss-breaks by
neutral or alkaline Comet assay) and tissues (in situ DNA
fragmentation by TUNEL or ISEL assays) combined, if
required, with quantitative immunocytochemistry and
intracellular localization of cell death-associated proteins
- Assessment of direct oxidative DNA
breaks and modifications
- Measurements of oxidative, membrane
damage and apoptotic markers using quantitative
immunocytochemistry
- Measurement of apoptotic
DNA-degrading enzymes activities
Technology Description
The mechanisms of toxic tissue injury and cell death underlie numerous
human diseases as well as the effects of pharmaceutical drugs and
environmental toxins. These mechanisms are complex and vary with tissue
structure, vascularization, spectrum of cell death proteins, nature of
damaging agent, the strength, length and frequency of the exposure to
the injury, and many other factors. Accordingly, cell death can take
forms of apoptosis, necrosis, autophagy, mitotic catastrophe, as well as
some intermediate or more specific forms of cell death including
aponecrosis, oncosis, anoikis or abortosis. To approach this complexity,
the best strategy for assessment of toxic tissue injury includes the use
of: a) common methods that occur in all injuries independent of causes,
mechanisms or the origin of tissue; b) methods that are quantitative;
and c) approaches that allow, if necessary, combining observations with
other methods to determine the mechanism of cell injury and death.
DNA fragmentation (i.e., accumulation of unprepared double-stranded DNA
breaks) is a form of DNA damage, which indicates that cell death reached
the point of no return and became irreversible. DNA fragmentation is a
hallmark of all types of cell death regardless of the mechanism. To
determine the mechanisms and molecules involved in cell death, DNA
fragmentation assays can be easily combined with immunocytochemistry.
Contact information:
DNA Damage & Toxicology Core
Biomedical Research Building I, Room B324
4301 West Markham Street
Mail Slot 638
Little Rock, AR 72205
Alexei Basnakian, M.D.,
Ph.D., Director
Department of Pharmacology & Toxicology
UAMS College of Medicine
basnakianalexeig@uams.edu
501-352-2870
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