PMID- 29968392 OWN - NLM STAT- MEDLINE DCOM- 20190111 LR - 20240210 IS - 1098-2280 (Electronic) IS - 0893-6692 (Print) IS - 0893-6692 (Linking) VI - 59 IP - 7 DP - 2018 Aug TI - Hepatic DNA damage in harbour porpoises (Phocoena phocoena) stranded along the English and Welsh coastlines. PG - 613-624 LID - 10.1002/em.22205 [doi] AB - 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 (32) P-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 10(8) 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. (c) 2018 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. CI - (c) 2018 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. FAU - Acevedo-Whitehouse, Karina AU - Acevedo-Whitehouse K AD - Institute of Zoology, Zoological Society of London, London, United Kingdom. AD - Unit for Basic and Applied Microbiology, Autonomous University of Queretaro, Queretaro, Mexico. FAU - Cole, Kathy J AU - Cole KJ AD - Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, United Kingdom. FAU - Phillips, David H AU - Phillips DH AUID- ORCID: 0000-0001-8509-3485 AD - Department of Analytical, Environmental and Forensic Sciences, MRC-PHE Centre for Environment and Health, King's College London, London, United Kingdom. AD - NIHR Health Protection Research Unit in Health Impact of Environmental Hazards at King's College London in partnership with Public Health England, London and Imperial College London, United Kingdom. FAU - Jepson, Paul D AU - Jepson PD AD - Institute of Zoology, Zoological Society of London, London, United Kingdom. FAU - Deaville, Rob AU - Deaville R AD - Institute of Zoology, Zoological Society of London, London, United Kingdom. FAU - Arlt, Volker M AU - Arlt VM AUID- ORCID: 0000-0003-4314-9318 AD - Department of Analytical, Environmental and Forensic Sciences, MRC-PHE Centre for Environment and Health, King's College London, London, United Kingdom. AD - NIHR Health Protection Research Unit in Health Impact of Environmental Hazards at King's College London in partnership with Public Health England, London and Imperial College London, United Kingdom. LA - eng GR - 14329/CRUK_/Cancer Research UK/United Kingdom GR - 101126/Z/13/Z/WT_/Wellcome Trust/United Kingdom GR - 101126/B/13/Z/WT_/Wellcome Trust/United Kingdom GR - C313/A14329/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180703 PL - United States TA - Environ Mol Mutagen JT - Environmental and molecular mutagenesis JID - 8800109 RN - 0 (Carcinogens, Environmental) RN - 0 (Mutagens) RN - 0 (Polycyclic Aromatic Hydrocarbons) RN - 0 (Water Pollutants, Chemical) RN - CIW5S16655 (DDT) RN - DFC2HB4I0K (Polychlorinated Biphenyls) RN - I0246D2ZS0 (Dieldrin) SB - IM MH - Animals MH - Carcinogens, Environmental/toxicity MH - DDT/toxicity MH - DNA Damage/*drug effects MH - Dieldrin/toxicity MH - England MH - Environmental Exposure/adverse effects MH - Environmental Monitoring MH - Female MH - Liver/*drug effects/enzymology/metabolism/pathology MH - Male MH - Mutagens/*toxicity MH - Phocoena/*genetics MH - Polychlorinated Biphenyls/*toxicity MH - Polycyclic Aromatic Hydrocarbons/*toxicity MH - Wales MH - Water Pollutants, Chemical/*toxicity PMC - PMC6174976 OTO - NOTNLM OT - 32P-postlabeling OT - DNA damage OT - genotoxicity OT - harbour porpoise OT - persistent organic pollutants (POPs) OT - polychlorinated biphenyls (PCBs) OT - polycyclic aromatic hydrocarbons (PAHs) EDAT- 2018/07/04 06:00 MHDA- 2019/01/12 06:00 PMCR- 2018/10/08 CRDT- 2018/07/04 06:00 PHST- 2018/02/02 00:00 [received] PHST- 2018/04/24 00:00 [revised] PHST- 2018/04/26 00:00 [accepted] PHST- 2018/07/04 06:00 [pubmed] PHST- 2019/01/12 06:00 [medline] PHST- 2018/07/04 06:00 [entrez] PHST- 2018/10/08 00:00 [pmc-release] AID - EM22205 [pii] AID - 10.1002/em.22205 [doi] PST - ppublish SO - Environ Mol Mutagen. 2018 Aug;59(7):613-624. doi: 10.1002/em.22205. Epub 2018 Jul 3.