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N. R. Jena et al.
3.1 Introduction
Several reactive species are continuously produced inside living cells during the
normal metabolic activities. Formation of these species in low concentration is beneficial for living cells as they are involved in mitogenic response, cellular signal
transduction, neurotransmission, blood pressure regulation etc. [1–3]. However, in
vivo overproduction of these reactive species can be quite harmful for living systems as they perturb structures and functions of important biomolecules such as
DNA, proteins and lipids severely. These reactive species can be subdivided into
three main categories, i.e. (1) reactive oxygen species (ROS), (2) reactive nitrogen
oxide species (RNOS), and (3) reactive halogen species (RHS). Oxygen in ROS,
nitrogen in RNOS, and the halogen atom in RHS are the main constituents that
readily react with different biomolecules in living systems. Although these reactive
species can damage almost all biomolecules in living cells, damages to DNA are
most abundant and harmful. As a consequence, several genotoxic and mutagenic
lesions are created which ultimately induce life degrading diseases such as aging,
cancer, neurodegenerative disorders including Alzheimer’s disease, Parkinson’s
disease, and acute central nervous system injuries [2, 4]. In addition to these in vivo
reactants, pre-solvated electrons [5, 6], other chemical agents [7], particularly pollutants [8], and high energy radiation [9–13] can also damage DNA by participating in complex biochemical reactions involving the various components of DNA.
Several drugs [14, 15] used for cancer therapy can also potentially interfere with
the normal functioning of DNA, thereby inducing other complicated diseases. It
should be noted that in comparison to exogenous factors, endogenous factors are
more responsible for the formation of several DNA damaged products which cause
different pathological consequences.
Damage to DNA can occur in various possible ways such as base modification [16–18], conformational changes, formation of abasic sites [19], DNA strand
breaks [20, 21], DNA strand cross-links [22, 23] and DNA-protein cross-links [24–
26]. Among all forms of DNA damage, base modifications by reactive species are
the simplest and very significant, following which a plethora of base lesions are
generated in cells. Occurrence of these base lesions is frequently observed in disease-prone cells and tissues, particularly in tumours [27, 28]. It is believed that the
various base lesions that are formed mainly due to oxidation of DNA accumulate in
both mitochondrial and nuclear DNA with increasing age. This accumulation followed by failure of cellular defence mechanisms to repair or excise different DNA
base lesions ultimately induces diseases. Not only these base lesions are capable of
directly generating stable mutations, cancer and other pathological conditions, they
can also be involved in the creation of several complicated processes indirectly by
participating in the formation of complex tandem lesions. For example, generation
of base damages in DNA can interfere with other bases on the same or the other
strand, thereby creating intra-strand or inter-strand crosslinks respectively. Similarly the interference of these base lesions with proteins can also create different
DNA-protein crosslink products [24–26].
N. R. Jena et al.
3.1 Introduction
Several reactive species are continuously produced inside living cells during the
normal metabolic activities. Formation of these species in low concentration is beneficial for living cells as they are involved in mitogenic response, cellular signal
transduction, neurotransmission, blood pressure regulation etc. [1–3]. However, in
vivo overproduction of these reactive species can be quite harmful for living systems as they perturb structures and functions of important biomolecules such as
DNA, proteins and lipids severely. These reactive species can be subdivided into
three main categories, i.e. (1) reactive oxygen species (ROS), (2) reactive nitrogen
oxide species (RNOS), and (3) reactive halogen species (RHS). Oxygen in ROS,
nitrogen in RNOS, and the halogen atom in RHS are the main constituents that
readily react with different biomolecules in living systems. Although these reactive
species can damage almost all biomolecules in living cells, damages to DNA are
most abundant and harmful. As a consequence, several genotoxic and mutagenic
lesions are created which ultimately induce life degrading diseases such as aging,
cancer, neurodegenerative disorders including Alzheimer’s disease, Parkinson’s
disease, and acute central nervous system injuries [2, 4]. In addition to these in vivo
reactants, pre-solvated electrons [5, 6], other chemical agents [7], particularly pollutants [8], and high energy radiation [9–13] can also damage DNA by participating in complex biochemical reactions involving the various components of DNA.
Several drugs [14, 15] used for cancer therapy can also potentially interfere with
the normal functioning of DNA, thereby inducing other complicated diseases. It
should be noted that in comparison to exogenous factors, endogenous factors are
more responsible for the formation of several DNA damaged products which cause
different pathological consequences.
Damage to DNA can occur in various possible ways such as base modification [16–18], conformational changes, formation of abasic sites [19], DNA strand
breaks [20, 21], DNA strand cross-links [22, 23] and DNA-protein cross-links [24–
26]. Among all forms of DNA damage, base modifications by reactive species are
the simplest and very significant, following which a plethora of base lesions are
generated in cells. Occurrence of these base lesions is frequently observed in disease-prone cells and tissues, particularly in tumours [27, 28]. It is believed that the
various base lesions that are formed mainly due to oxidation of DNA accumulate in
both mitochondrial and nuclear DNA with increasing age. This accumulation followed by failure of cellular defence mechanisms to repair or excise different DNA
base lesions ultimately induces diseases. Not only these base lesions are capable of
directly generating stable mutations, cancer and other pathological conditions, they
can also be involved in the creation of several complicated processes indirectly by
participating in the formation of complex tandem lesions. For example, generation
of base damages in DNA can interfere with other bases on the same or the other
strand, thereby creating intra-strand or inter-strand crosslinks respectively. Similarly the interference of these base lesions with proteins can also create different
DNA-protein crosslink products [24–26].