Page 908 - The Toxicology of Fishes

888 The Toxicology of Fishes

A B C D

Reference 1,200 5,600 19,000
Sediment
(ng ΣPAHs/g Sediment)
Laboratory Exposure
E F G

Eagle Harbor Pilot Point Eagle Harbor
Sediment Extract Reference Site Contaminated Site
Injection Exposure Field Exposure
FIGURE 22.6 Computer-generated images of hepatic DNA digests analyzed by the P-postlabeling method for English
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sole exposed for 5 weeks to PAH-contaminated sediments (concentrations of ΣPAHs are (A) 20 ng/g sediment, (B) 1200
ng/g sediment, (C) 5600 ng/g sediment, and (D) 1900 ng/g sediment. Images are also shown for (E) English sole injected
intramuscularly with an organic solvent extract of contaminated Eagle Harbor sediment and (G) English sole captured from
Eagle Harbor. Hepatic DNA adducts were not observed on images of English sole captured from (F) the reference site,
Pilot Point. (From French, B.L. et al., Aquat. Toxicol., 36, 1–16, 1996. With permission.)

and thus is a useful epidemiological/epizootiological tool for detecting exposure to genotoxins. Second,
DNA adduct levels integrate multiple toxicokinetic factors (i.e., uptake, metabolism, detoxication, excre-
tion, and covalent binding of reactive metabolites to target tissues). Third, the DNA adduct profiles and
levels can be used in identifying species differences in exposure and processing of genotoxic compounds.
Hepatic DNA adducts are currently being used as a marker of exposure to potentially genotoxic
contaminants in environmental monitoring of Puget Sound and have been applied in national monitoring
programs, such as the National Benthic Surveillance Project of the National Oceanographic and Atmo-
spheric Administration (NOAA) National Status and Trends (NS&T) Program and in the Bioeffects
Surveys of NOAA’s Coastal Ocean Program. The International Council for the Exploration of the Sea
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(ICES) has recently published a methods manual on the P-postlabeling assay to encourage its use in
marine biomonitoring studies (Reichert et al., 1999).
Other investigators have also detected DNA damage in English sole from Puget Sound sites with
different assessment techniques. Using GC–MS with selected ion monitoring (GC–MS/SIM) and Fourier-
transform infrared (FT–IR) spectroscopy, Malins and colleagues (Malins and Gunselman, 1994; Malins
et al., 1996, 1997) have observed hydroxy-radical-induced DNA damage in liver tissue of English sole
from contaminated sites in Puget Sound (e.g., the Duwamish Waterway). Common types of damage
included hydroxyl-radical-induced ring-opening products (e.g., 2,6-diamino-4-hydroxy-5-formamidopy-
rimidine) and 8-hydroxy adducts of adenine and guanine (e.g., 8-hydroxyguanine). These mutagenic
base modifications were statistically correlated with an increased incidence of preneoplastic or degen-
erative liver lesions (e.g., basophilic foci, hepatocellular karyomegaly, megalocytic hepatosis, hyalin
droplet formation, and apoptosis) in English sole (Malins et al., 1996).
Related forms of oxidative damage have been detected in juvenile salmonids exposed to dietary PAHs
in the laboratory (Bravo, 2005). Juvenile rainbow trout (Oncorhynchus mykiss) fed a diet containing a
mixture of 10 common HAHs at 40 or 400 mg/kg, 160 mg/kg BaP, or 160 mg/kg benzo(e)pyrene had
induced CYP1A1 in liver and kidney and increased oxidative damage as indicated by DNA strand breaks
measured in blood by comet assay, protein nitration measured in kidney by immunohistochemistry, and