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

Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8800109 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-2280 (Electronic) Linking ISSN: 08936692 NLM ISO Abbreviation: Environ Mol Mutagen Subsets: MEDLINE

Publication: New York Ny : Wiley-Liss
Original Publication: New York, NY : Liss, c1987-

Carcinogenesis/*chemically induced ; DNA Adducts/*toxicity ; DNA Damage/*drug effects ; Epithelial Cells/*pathology ; Gastrointestinal Neoplasms/*etiology ; Gastrointestinal Neoplasms/*pathology ; Intestinal Mucosa/*pathology ; Polycyclic Aromatic Hydrocarbons/*toxicity; Animals ; Arctic Regions ; Beluga Whale ; Fibroblasts/drug effects ; Fibroblasts/pathology ; Intestinal Mucosa/cytology ; Mice ; Water Pollutants, Chemical/toxicity

Carcinogenic polycyclic aromatic hydrocarbons (PAHs) were disposed directly into the Saguenay River of the St. Lawrence Estuary (SLE) by local aluminum smelters (Quebec, Canada) for 50 years (1926-1976). PAHs in the river sediments are likely etiologically related to gastrointestinal epithelial cancers observed in 7% of 156 mature (>19-year old) adult beluga found dead along the shorelines. Because DNA adduct formation provides a critical link between exposure and cancer induction, and because PAH-DNA adducts are chemically stable, we hypothesized that SLE beluga intestine would contain PAH-DNA adducts. Using an antiserum specific for DNA modified with several carcinogenic PAHs, we stained sections of paraffin-embedded intestine from 51 SLE beluga (0-63 years), 4 Cook Inlet (CI) Alaska beluga (0-26 years), and 20 beluga (0-46 years) living in Arctic areas (Eastern Beaufort Sea, Eastern Chukchi Sea, Point Lay Alaska) and aquaria, all with low PAH contamination. Stained sections showed nuclear light-to-dark pink color indicating the presence of PAH-DNA adducts concentrated in intestinal crypt epithelial lining cells. Scoring of whole tissue sections revealed higher values for the 51 SLE beluga, compared with the 20 Arctic and aquarium beluga (P = 0.003). The H-scoring system, applied to coded individual photomicrographs, confirmed that SLE beluga and CI beluga had levels of intestinal PAH-DNA adducts significantly higher than Arctic and aquarium beluga (P = 0.003 and 0.02, respectively). Furthermore, high levels of intestinal PAH-DNA adducts in four SLE beluga with gastrointestinal cancers, considered as a group, support a link of causality between PAH exposure and intestinal cancer in SLE beluga. Environ. Mol. Mutagen. 60:29-41, 2019. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
(Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

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Z01 BC005177-27 United States Intramural NIH HHS; Z01 BC 005177 United States CA NCI NIH HHS

Keywords: Delphinapterus leucas; PAHs; cancer; cetaceans; chemical carcinogens; pollutants

0 (DNA Adducts)
0 (Polycyclic Aromatic Hydrocarbons)
0 (Water Pollutants, Chemical)
0 (polycyclic aromatic hydrocarbons-DNA adduct)

Date Created: 20181012 Date Completed: 20190214 Latest Revision: 20231005

20240829

PMC6320268

10.1002/em.22251

30307653