Effects of Dioxins and Related Compounds in the Liver of Wild Baikal Seals: An Implication from a Toxicogenomic Approach

Abstract—Dioxins and related compounds (DRCs) including polychlorinated dibenzo-p-dioxins, dibenzofurans and coplanar polychlorinated biphenyls are highly accumulated in the liver of Baikal seals (Pusa sibirica). The hepatic DRC levels were positively correlated with expression levels of CYP1A1, 1A2 and 1B1 in the wild population, indicating chronic induction of these CYP isozymes by DRCs. To screen DRC-responsive genes other than CYP1 isozymes, we constructed an oligo array of targeting genes expressed in the liver of wild Baikal seals, and examined the relationships between the hepatic DRC levels and gene expression levels. The result indicated that dioxins may affect the expression of genes involved in xenobiotic metabolism, oxidative stress, Fe ion homeostasis and immune response in the liver of Baikal seals. The mRNA expression levels of CYP1 isozymes were positively correlated with genes related to oxidative stress (thioredoxin and selenoprotein P precursor) and Fe ion homeostasis (ferritin and hepcidin). In addition, CYP1A2 mRNA expression levels positively correlated with the levels of malondialdehyde, a biomarker of oxidative stress. From these results, we propose that Baikal seals may suffer from effects initiated by dioxin-induced CYP1 isozymes, including production of reactive oxygen species, release of free Fe ion from heme degradation and induction of inflammatory response