Biology Reference
In-Depth Information
(iv) Electrochemical determination of the length of guanine-
containing triplet repeats was achieved by the mediator-based
guanineelectrocatalyticoxidationtechnique.Otherapproaches
applied for this purpose involve multiple hybridization of a
labeled RP spanning several triplet units with the expanded
triplet repeat [25]. The number of RP molecules hybridized
(or labels collected) per tDNA strand is proportional to the
length of the repetitive sequence, which is - after proper
normalization to the number of target strands - reflected by
intensity of the measured signal.
1.3.2
DNA Damage
As DNA belongs to main body substrates that undergo serious
structural changes such as oxidation of the DNA bases and sugar
moieties and/or release of the bases as well as DNA strand breaks
caused by chemical systems generating so-called reactive oxygen
(ROS), nitrogen (RNS), or sulfur (RSS) species [35, 36] and by other
classes of genotoxic substances [37], the second main application
area of DNA-based biosensors is detection of damage to DNA. ROS
are produced endogenously, during normal aerobic metabolism
and under various pathological conditions, and exogenously, such
as upon exposure to UV light, ionizing radiation, environmental
mutagens, and carcinogens. About 10
4
to 10
6
DNA damage events
occur to a cell per day [37]. Accumulation of oxidative DNA lesions
is associated with aging and with a variety of human diseases,
including cancer and neurodegeneration. The terms
DNA damage
(see below) and
mutation
should not be intermingled. While
mutation refers to a change in DNA sequence, in damaged DNA
the chemical nature of individual nucleotides is changed, which can
result in mutation.
Altered chemical, physicochemical, and structural properties of
damaged DNA are reflected in its redox behavior, which is utilized
in numerous techniques of DNA damage detection. Electrochemical
DNA-based biosensors have been used not only to detect but also
to induce and control DNA damage at the electrode surface via
electrochemicalgenerationofthedamaging(usuallyradical)species
[13].Thisway,chemicalsanddrugssuchasniclosamide,adriamycin,
