latter is metabolized to O 2 and water by the action of CAT and GPx enzymes
[24]. The balance between prooxidant and antioxidant molecules and ROS sequestration is crucial to maintain cell homeostasis [25].
Genotoxicity can be defined as the damage generated to DNA; DNA damage
includes chain breaks, sugar damage, modifications, or loss in the bases and crosslinks [7, 26]. 8-Hydroxydeoxyguanosine, an oxidized form of guanine, is the main
oxidative product of DNA damage that can cause mutations [27]. However, to
counteract DNA damage, cells activate at least five specific repair pathways, including base excision repair, nucleotide excision repair, mismatch repair, homologous
recombination, and nonhomologous end joining, which are activated at different
stages of the cell cycle, allowing cells to repair DNA damage [7]. Micronuclei are
extranuclear chromosomal fragments, which are caused by defects in cell division
and errors in DNA replication or repair [28, 29]. When DNA damage is persistent,
programmed cell death or apoptosis, a regulatory response to DNA damage, is
activated to eliminate cells with genomic instability [30].
Cellular cytotoxicity refers to the ability of certain chemical substances to
alter basic cellular functions and cause the destruction of living cells [31]. DNA
damage induces expression of the tumor suppressor protein p53. The increase in
this protein causes the expression of pro-apoptotic proteins of the Bcl-2 family (Bax
and PUMA), which promote changes in the mitochondria with the release of
cytochrome c. This compound leaves the mitochondria and activates the cascade
of caspases [26, 32]. Caspases are a family of proteins belonging to the group of
cysteine proteases, essential mediators of apoptosis processes. Caspase-3 activation
is the point where the intrinsic or mitochondrial pathway and the extrinsic or death
receptor pathway converge, resulting in DNA fragmentation, degradation of cytoskeletal and nuclear proteins, protein cross-linking, formation of apoptotic bodies,
ligand expression for phagocytic cell receptors, and absorption by phagocytic
cells [30].
3 Biomarkers and Bioindicators
A biomarker is defined as a quantifiable change in the biological response (cellular
and molecular), as well as physiological and histopathological alterations and even
behavioral changes, which may be related to the toxic effects or exposure of
chemicals that are present in the environment [33]. These can be classified into
three groups [24, 34]:
(a) Exposure biomarkers: they contemplate the detection and calculation of exogenous substances or their metabolites or the product of an interaction between a
xenobiotic and some target molecule or cell, which is measured in a
108
N. SanJuan-Reyes et al.
[24]. The balance between prooxidant and antioxidant molecules and ROS sequestration is crucial to maintain cell homeostasis [25].
Genotoxicity can be defined as the damage generated to DNA; DNA damage
includes chain breaks, sugar damage, modifications, or loss in the bases and crosslinks [7, 26]. 8-Hydroxydeoxyguanosine, an oxidized form of guanine, is the main
oxidative product of DNA damage that can cause mutations [27]. However, to
counteract DNA damage, cells activate at least five specific repair pathways, including base excision repair, nucleotide excision repair, mismatch repair, homologous
recombination, and nonhomologous end joining, which are activated at different
stages of the cell cycle, allowing cells to repair DNA damage [7]. Micronuclei are
extranuclear chromosomal fragments, which are caused by defects in cell division
and errors in DNA replication or repair [28, 29]. When DNA damage is persistent,
programmed cell death or apoptosis, a regulatory response to DNA damage, is
activated to eliminate cells with genomic instability [30].
Cellular cytotoxicity refers to the ability of certain chemical substances to
alter basic cellular functions and cause the destruction of living cells [31]. DNA
damage induces expression of the tumor suppressor protein p53. The increase in
this protein causes the expression of pro-apoptotic proteins of the Bcl-2 family (Bax
and PUMA), which promote changes in the mitochondria with the release of
cytochrome c. This compound leaves the mitochondria and activates the cascade
of caspases [26, 32]. Caspases are a family of proteins belonging to the group of
cysteine proteases, essential mediators of apoptosis processes. Caspase-3 activation
is the point where the intrinsic or mitochondrial pathway and the extrinsic or death
receptor pathway converge, resulting in DNA fragmentation, degradation of cytoskeletal and nuclear proteins, protein cross-linking, formation of apoptotic bodies,
ligand expression for phagocytic cell receptors, and absorption by phagocytic
cells [30].
3 Biomarkers and Bioindicators
A biomarker is defined as a quantifiable change in the biological response (cellular
and molecular), as well as physiological and histopathological alterations and even
behavioral changes, which may be related to the toxic effects or exposure of
chemicals that are present in the environment [33]. These can be classified into
three groups [24, 34]:
(a) Exposure biomarkers: they contemplate the detection and calculation of exogenous substances or their metabolites or the product of an interaction between a
xenobiotic and some target molecule or cell, which is measured in a
108
N. SanJuan-Reyes et al.