Biology Reference
In-Depth Information
Alkylating agents, active metabolites of xenobiotics such as polycyclic aromatic hydro-
carbons (PAHs), and endogenous active radicals may bind covalently to DNA and form
adducts. Lipid peroxidation products, such as aldehydes, covalently modify lipids, pro-
teins, and DNA, whose nucleophilic groups present in purine and pyrimidine bases are
targets for electrophilic moieties (Nair 1999). Etheno-adducts are biomarkers of DNA
damage arising from the reaction of lipid peroxidation end products, and recognized as a
typical signature of DNA damage in white blood cells (Arab et al. 2009). Despite the bio-
logical relevance of these adducts, shown to be mutagenic in bacteria, there are few studies
measuring DNA adducts generated by oxidative stress in aquatic model organisms. The
first analyses of etheno-adducts in tissues of the mussel
Perna perna
were conducted by
Almeida et al. (2006), who checked for effects of seasonality in the mantle and in the diges-
tive gland. The method of analysis of these adducts using high-performance liquid chro-
matography coupled to mass spectrometry (HPLC-MS) has been described by Machado
Garcia et al. (2012).
DNA adducts have been used for two decades as a molecular dosimetric index by the
National Oceanic and Atmospheric Administration (NOAA) for studying factors of toxico-
pathic liver lesions in fish, including neoplasms. Populations at risk include flatfish, which
are bottom-feeding fish species living in close contact with sediments. They accumulate a
variety of contaminants from sediments, which are a known repository for a large number
of inorganic and organic hydrophobic pollutants. A large monitoring program of sedi-
ment and bottom fish for chlorinated hydrocarbon pesticides, polychlorobiphenyls (PCBs),
and PAHs was launched along the west coast of the United States, from 1984 to 1993, in
order to identify factors of fish disease and establish remediation. The studied species on
U.S. coasts included
Pleuronectes vetulus
(English sole),
Platichthys stellatus
(starry flounder),
Genyonemus lineatus
(white croaker) on the Pacific coast, and
Pleuronectes americanus
(win-
ter flounder) on the northeast coast (Myers et al. 1998a).
The goals were to identify pollutants responsible for the adverse effects recorded and to
validate biomarkers of neoplastic and nonneoplastic lesions (Chapter 15). Hepatic lesions
included proliferation, specific degeneration/necrosis, foci of cellular alterations, and neo-
plasms (Myers et al. 2003). PAH pollutants were identified among risk factors, whereas
PCBs were only detected as potentially PAH-interacting agents (Myers et al. 1990). Liver
lesions could be related with hepatic DNA adducts or biliary fluorescent aromatic com-
pounds (FACs) representing PAH metabolites released into the bile. Liver lesions, however,
did not correlate well with levels of sediment contamination.
DNA adducts have been validated as biomarkers in more than 28 teleost fish species
(Reichert et al. 1998). Exposure to a mixture of polyaromatic compounds leads to typical
autoradiographic patterns of hepatic DNA digests that distribute within a diagonal on
thin layer chromatograph maps. The “diagonal radioactive zone” results from spots of
DNA adducts of different molecular weights produced by PAH metabolites (Varanasi et
al. 1989).
Hepatic DNA adducts are rapidly formed within 24-48 h of exposure (Collier and
Varanasi 1991). They also have slow repair rates (French et al. 1996) with estimated half-
lives of 40-100 days in English sole. Therefore, the biomarker is considered a reliable and
useful dose-responsive indicator of cumulative and chronic exposure to PAHs in wild fish.
On the other hand, FACs, which are rapidly eliminated from fish, reflect recent exposure to
PAH-contaminated sediment. This FAC biomarker of short-term PAH exposure responds
within hours, is dose-responsive, reaches a maximum within 2 weeks in conditions of
continuous exposure, and has a half-life of 14-16 days in English sole (Collier and Varanasi
1991; French et al. 1996).
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