title: Effects of persistent organochlorine exposure on the liver transcriptome of the common minke whale (Balaenoptera acutorostrata) from the North Pacific.
abstract: Hepatic concentrations of persistent organochlorines (OCs) were determined in the common minke whale (Balaenoptera acutorostrata) from the North Pacific. To investigate the effects of OCs on the transcriptome in the minke whale, the present study constructed a hepatic oligo array of this species where 985 unique oligonucleotides were spotted and further analyzed the relationship between the OC levels and gene expression profiles of liver tissues. The stepwise multiple linear regression analysis identified 32 genes that correlated with hepatic OC levels. The mRNA expression levels of seven cytochrome P450 (CYP) genes, CYP1A1, 1A2, 2C78, 2E1, 3A72, 4A35, and 4V6 showed no clear correlations with the concentration of each OC, suggesting that the accumulated OCs in the liver did not reach levels that could alter CYP expression. Among the genes screened by the custom oligo array analysis, hepatic mRNA expression levels of 16 genes were further measured using quantitative real-time reverse transcription polymerase chain reaction. The mRNA levels of vitamin D-binding protein (DBP) were negatively correlated with non-ortho coplanar polychlorinated biphenyl (PCB) levels. Androgen receptor-associated coregulator 70 (ARA70) expression levels showed a significant positive correlation with concentrations of non-ortho coplanar PCB169. These correlations suggest that coplanar PCB-reduced DBP expression could suppress vitamin D receptor-mediated signaling cascades in peripheral tissues. Alternatively, the suppression of vitamin D receptor signaling cascade could be enhanced through competition with the androgen receptor signaling pathway for ARA70. In addition, a negative correlation between kynureninase and PCB169 levels was also observed, which suggest an enhanced accumulation of an endogenous aryl hydrocarbon receptor agonist, kynurenine in the minke whale population. Further studies are necessary to translate the changes in the transcriptome to toxicological outcomes including the disruption of the nervous and immune systems.
authors.affiliation: Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Niimi
authors.affiliation: Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Imoto
authors.affiliation: Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kunisue
authors.affiliation: Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan.
authors.forename: Michio X
authors.initials: MX
authors.lastname: Watanabe
authors.affiliation: Department of Life and Nanopharmaceutical Science and Department of Biology, Kyung Hee University, Hoegi-Dong, Dongdaemun-Gu, Seoul 130-701, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: The Institute of Cetacean Research, Toyomi-cho 4-5, Chuo-ku, Tokyo 104-0055, Japan.
authors.forename: Genta
authors.initials: G
authors.lastname: Yasunaga
authors.affiliation: The Institute of Cetacean Research, Toyomi-cho 4-5, Chuo-ku, Tokyo 104-0055, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujise
authors.affiliation: Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Tanabe
authors.affiliation: Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan. Electronic address: iwatah@agr.ehime-u.ac.jp.
authors.forename: Hisato
authors.initials: H
authors.lastname: Iwata
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D020869:Gene Expression Profiling; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism / Q000633:toxicity*; D007564:Japan; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D050636:Minke Whale / Q000378:metabolism*; D010140:Pacific Ocean; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D059467:Transcriptome
chemical_list: D006843:Hydrocarbons, Chlorinated; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C027309:3,4,5,3',4',5'-hexachlorobiphenyl
keywords: Dioxins; Kynureninase; Minke whale; Organochlorines; Transcriptome