506
29.3.7 Oxidative Stress and DNA Damage
Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the organism’s ability to detoxify reactive intermediates, such as those generated by metabolism of PAHs through cytochrome P450.
Depending on the severity of oxidative stress, this imbalance between excessive
production of ROS and antioxidant defenses can lead to lipid peroxidation (LPO),
resulting from a suite of chain reactions triggered by radicals causing loss of membrane integrity and DNA damage. Potential damage to DNA can be caused by a
variety of mechanistic endpoints, such as oxidized bases, apurinic/apyrimidinic
sites, single- or double-strand breaks, and formation of DNA adducts, in which PAH
metabolites intercalate into the DNA (Xue and Warshawsky 2005; Starostenko et al.
2017).
Monitoring organismal antioxidant defenses as markers for oxidative stress due
to PAH exposure in fish is relatively new. The antioxidant enzymes, superoxide
dismutase (SOD), and catalase (CAT) activities have been extensively used as biomarkers for a variety of contaminants; however direct links could not be established
for SOD-CAT activities to a specific class of contaminants including PAHs (van der
Oost et al. 2003), rendering these ineffective as markers for PAH-associated oxidative stress. Reduced glutathione (GSH), an important non-enzymatic antioxidant,
acts as a scavenger for ROS (particularly H 2 O 2 ) and PAH reactive intermediates to
produce oxidized glutathione (GSSG), which is then recycled back to GSH for antioxidant defense. The relationship of PAH exposure and associated oxidative stress
has been established using GSH/GSSG for antioxidant defense assessments. Other
useful assessments of oxidative stress include measuring levels of malondialdehyde
(MDA; a by-product of LPO), lipid hydroperoxides, and the total antioxidant capacity (TAC). In nuclear and mitochondrial DNA, 8-hydroxy-2-deoxyguanosine
(8-OHdG) is one of the predominant forms of free radical-induced oxidative lesions
and it has been widely used as a biomarker for oxidative stress leading to DNA
oxidative damage.
In a series of controlled DWH surrogate oil exposures, targeted GoM fish species
exhibited an overall decrease in antioxidants, increase of lipid peroxidation, and
evidence of DNA damage. A correlation of ∑50PAH in the liver and decrease in
antioxidant defense was observed in Florida pompano exposed to CEWAF concentrations of 14.7 μg/L∑50PAH (Wetzel DOI: 10.7266/N7PZ5793). Red drum experienced a significant reduction in antioxidant defenses, increase in lipid peroxidation,
a decrease in total antioxidant capacity, and a slight (not significant) increase in liver
DNA oxidative damage (8-OHdG) when exposed to 485.07 mg/kg∑50PAH and
688.94 mg/kg∑50PAH DWH surrogate oil- contaminated feed for 14 days (Wetzel
DOI: 10.7266/N7Q23XRS). Similarly, effects of oxidative stress were observed in
southern flounder exposed to 47.50 mg/kg∑50PAH DWH surrogate oiled sediment
for 30 days (Wetzel DOI: 10.7266/N7WH2NGJ). In a laboratory study using adult
Gulf killifish, genotoxicity was observed in the form of single-stranded DNA
M. Grosell et al.
29.3.7 Oxidative Stress and DNA Damage
Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the organism’s ability to detoxify reactive intermediates, such as those generated by metabolism of PAHs through cytochrome P450.
Depending on the severity of oxidative stress, this imbalance between excessive
production of ROS and antioxidant defenses can lead to lipid peroxidation (LPO),
resulting from a suite of chain reactions triggered by radicals causing loss of membrane integrity and DNA damage. Potential damage to DNA can be caused by a
variety of mechanistic endpoints, such as oxidized bases, apurinic/apyrimidinic
sites, single- or double-strand breaks, and formation of DNA adducts, in which PAH
metabolites intercalate into the DNA (Xue and Warshawsky 2005; Starostenko et al.
2017).
Monitoring organismal antioxidant defenses as markers for oxidative stress due
to PAH exposure in fish is relatively new. The antioxidant enzymes, superoxide
dismutase (SOD), and catalase (CAT) activities have been extensively used as biomarkers for a variety of contaminants; however direct links could not be established
for SOD-CAT activities to a specific class of contaminants including PAHs (van der
Oost et al. 2003), rendering these ineffective as markers for PAH-associated oxidative stress. Reduced glutathione (GSH), an important non-enzymatic antioxidant,
acts as a scavenger for ROS (particularly H 2 O 2 ) and PAH reactive intermediates to
produce oxidized glutathione (GSSG), which is then recycled back to GSH for antioxidant defense. The relationship of PAH exposure and associated oxidative stress
has been established using GSH/GSSG for antioxidant defense assessments. Other
useful assessments of oxidative stress include measuring levels of malondialdehyde
(MDA; a by-product of LPO), lipid hydroperoxides, and the total antioxidant capacity (TAC). In nuclear and mitochondrial DNA, 8-hydroxy-2-deoxyguanosine
(8-OHdG) is one of the predominant forms of free radical-induced oxidative lesions
and it has been widely used as a biomarker for oxidative stress leading to DNA
oxidative damage.
In a series of controlled DWH surrogate oil exposures, targeted GoM fish species
exhibited an overall decrease in antioxidants, increase of lipid peroxidation, and
evidence of DNA damage. A correlation of ∑50PAH in the liver and decrease in
antioxidant defense was observed in Florida pompano exposed to CEWAF concentrations of 14.7 μg/L∑50PAH (Wetzel DOI: 10.7266/N7PZ5793). Red drum experienced a significant reduction in antioxidant defenses, increase in lipid peroxidation,
a decrease in total antioxidant capacity, and a slight (not significant) increase in liver
DNA oxidative damage (8-OHdG) when exposed to 485.07 mg/kg∑50PAH and
688.94 mg/kg∑50PAH DWH surrogate oil- contaminated feed for 14 days (Wetzel
DOI: 10.7266/N7Q23XRS). Similarly, effects of oxidative stress were observed in
southern flounder exposed to 47.50 mg/kg∑50PAH DWH surrogate oiled sediment
for 30 days (Wetzel DOI: 10.7266/N7WH2NGJ). In a laboratory study using adult
Gulf killifish, genotoxicity was observed in the form of single-stranded DNA
M. Grosell et al.