Poirier Miriam C, Lair Stéphane, Michaud Robert, Hernández-Ramon Elena E, Divi Kathyayini V, Dwyer Jennifer E, Ester Corbin D, Si Nancy N, Ali Mehnaz, Loseto Lisa L, Raverty Stephen A, St Leger Judith A, Van Bonn William G, Colegrove Kathleen, Burek-Huntington Kathleen A, Suydam Robert, Stimmelmayr Raphaela, Wise John Pierce, Wise Sandra S, Beauchamp Guy, Martineau Daniel
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Canadian Wildlife Health Cooperative, Département de pathologie et microbiologie, Faculté de médecine vétérinaire, Université de Montréal, St. Hyacinthe, PQ, J2S2M2, Canada.
Environ Mol Mutagen. 2019 Jan;60(1):29-41. doi: 10.1002/em.22251. Epub 2018 Oct 11.
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.
当地的铝冶炼厂（加拿大魁北克）在50年的时间里（1926年至1976年）一直将致癌性多环芳烃（PAHs）直接排放到圣劳伦斯河口（SLE）的萨格奈河中。在沿着海岸线发现死亡的156头成熟（年龄大于19岁）成年白鲸中，有7%患有胃肠道上皮癌，河流沉积物中的PAHs可能在病因上与此有关。由于DNA加合物的形成在暴露与癌症诱发之间提供了关键联系，并且由于PAH-DNA加合物在化学上是稳定的，我们推测SLE白鲸的肠道中会含有PAH-DNA加合物。我们使用一种对几种致癌性PAHs修饰的DNA具有特异性的抗血清，对51头SLE白鲸（年龄0至63岁）、4头阿拉斯加库克湾（CI）白鲸（年龄0至26岁）以及20头生活在北极地区（东波弗特海、楚科奇海东部、阿拉斯加利角）和水族馆中的白鲸（年龄0至46岁）的石蜡包埋肠道切片进行染色，所有这些白鲸的PAH污染水平都很低。染色切片显示细胞核呈现从浅粉色到深粉色，表明PAH-DNA加合物存在于肠道隐窝上皮衬里细胞中。对整个组织切片进行评分发现，与20头北极和水族馆白鲸相比，51头SLE白鲸的得分更高（P = 0.003）。应用于编码的个体显微照片的H评分系统证实，SLE白鲸和CI白鲸肠道中的PAH-DNA加合物水平显著高于北极和水族馆白鲸（分别为P = 0.003和0.02）。此外，将患有胃肠道癌症的4头SLE白鲸作为一组来看，其肠道中高水平的PAH-DNA加合物支持了PAH暴露与SLE白鲸肠道癌症之间的因果联系。《环境与分子诱变》60:29 - 41，2019年。2018年发表。本文是美国政府作品，在美国属于公共领域。
