Hepatic DNA damage in harbour porpoises (Phocoena phocoena) stranded along the English and Welsh coastlines

Abstract

One level at which persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons PAHs) can exert damage is by causing DNA strand‐breaks or nucleotide base modifications, which, if unrepaired, can lead to embryonic mutations, abnormal development and cancer. In marine ecosystems, genotoxicity is expected to be particularly strong in long‐lived apex predators due to pollutant bioaccumulation. We conducted 32P‐postlabeling analyses optimized for the detection and quantification of aromatic/hydrophobic DNA adducts in the livers of 40 sexually‐mature North Atlantic harbour porpoises (Phocoena phocoena) stranded along the English and Welsh coastlines. We examined hepatic tissue to search for inflammatory and preneoplastic lesions and examine their association with adduct levels. Adducts were found in all porpoises (mean: 17.56 ± 11.95 per 108 nucleotides), and were higher than levels reported for marine vertebrates from polluted sites. The pollutants causing the induced DNA adducts could not be further characterized. Hepatic DNA damage did not correlate with levels of blubber POP concentrations (including total polychlorinated biphenyl [PCBs], dichlorodiphenyltrichloroethane [DDT] and dieldrin); PAH concentrations were not available for the present study. However, DNA damage predicted occurrence of inflammatory and preneoplastic lesions. Further, our data showed a reduction in hepatic DNA adduct levels with age in the 40 animals examined while POP concentrations, particularly PCBs, increased with age. Using a different dataset of 145 mature male harbour porpoises confirmed that higher contaminant levels (total PCBs, DDT and dieldrin) are found in older animals. The reduction in hepatic DNA adduct levels in older animals was in accordance with other studies which show that suppression of hepatic CYP1A enzyme activity at high PCB concentrations might impact on CYP1A‐mediated DNA adduct formation of PAHs which are ubiquitous environmental pollutants and readily metabolized by CYP1A to species binding to DNA. In summary, our study shows that pollutant‐induced DNA damage is prevalent in harbour porpoises from UK waters and may lead to detectable sub‐lethal hepatic damage. Environ. Mol. Mutagen. 59:613–624, 2018. © 2018 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society

Intestinal polycyclic aromatic hydrocarbon‐DNA adducts in a population of beluga whales with high levels of gastrointestinal cancers

“…A great deal of published evidence links PAH exposures, PAH-DNA adducts, and cancer risk in experimental animal models and humans [Culp and Beland, 1994;Culp et al, 2000;Poirier, 2004;Gunter et al, 2007;WHO, 2012]. Stranded harbour porpoises in the UK were recently found to have bulky DNA adducts in liver [Acevedo-Whitehouse et al, 2018]. DNA adducts are necessary but not sufficient for a tumor to form, and tumorigenesis is organ-specific, often requiring additional factors such as inflammation and cell proliferation, for mutation fixation in critical genes.…”

Immune Responses of the Critically Endangered Yangtze Finless Porpoises (Neophocaena asiaeorientalis ssp. asiaeorientalis) to Escalating Anthropogenic Stressors in the Wild and Seminatural Environments

“…Pollutants like pesticides and poultry excrement have been entering the TZO for over 20 years. These chemicals can negatively affect the liver profile and other physiological processes in YFPs (Acevedo-Whitehouse et al, 2018). Similarly, a significantly high expression level of FTL in the YFPs living in the TZO also indicates an immunomodulatory response (Zarjou et al, 2019).…”

In vivo localization and postmortem stability of benzo[a]pyrene‐DNA adducts

“…Evidence points to PAH‐DNA adduct formation as an essential step in human gastrointestinal cancer etiology (Sinha et al ; van Gijssel et al ; Gunter et al ). There is also evidence that, in marine mammal populations, exposure to carcinogenic PAHs can lead to increased cancer risk through the formation of PAH‐DNA adducts (Martineau et al ; Lair et al ; Acevedo‐Whitehouse et al ; Poirier et al ). In our previous study (Poirier et al ), we documented high PAH‐DNA adduct levels in small intestines of beluga whales living in the St. Lawrence estuary, an area with high PAH contamination and where beluga have been affected by high rates of cancers.…”

“…In this study, the persistence of BPdG adducts in mouse postmortem tissues has proven the feasibility of studying PAH‐DNA adducts in wildlife species living in relatively cold climates. A few studies notwithstanding (Martineau et al ; Acevedo‐Whitehouse et al ; Poirier et al ), very little is currently known regarding mechanisms underlying PAH exposures in wildlife. Here we found that PAH‐DNA adducts are unchanged up to 7 days postmortem, long after autolytic and bacterial degradation of intestinal tissue blurred extensively the tissue architecture.…”