title: Profiling of biomarkers for the exposure of polycyclic aromatic hydrocarbons: lamin-A/C isoform 3, poly[ADP-ribose] polymerase 1, and mitochondria copy number are identified as universal biomarkers.
abstract: This study investigated the profiling of polycyclic aromatic hydrocarbon- (PAH-) induced genotoxicity in cell lines and zebrafish. Each type of cells displayed different proportionality of apoptosis. Mitochondrial DNA (mtDNA) copy number was dramatically elevated after 5-day treatment of fluoranthene and pyrene. The notable deregulated proteins for PAHs exposure were displayed as follows: lamin-A/C isoform 3 and annexin A1 for benzopyrene; lamin-A/C isoform 3 and DNA topoisomerase 2-alpha for pentacene; poly[ADP-ribose] polymerase 1 (PARP-1) for fluoranthene; and talin-1 and DNA topoisomerase 2-alpha for pyrene. Among them, lamin-A/C isoform 3 and PARP-1 were further confirmed using mRNA and protein expression study. Obvious morphological abnormalities including curved backbone and cardiomegaly in zebrafish were observed in the 54 hpf with more than 400 nM of benzopyrene. In conclusion, the change of mitochondrial genome (increased mtDNA copy number) was closely associated with PAH exposure in cell lines and mesenchymal stem cells. Lamin-A/C isoform 3, talin-1, and annexin A1 were identified as universal biomarkers for PAHs exposure. Zebrafish, specifically at embryo stage, showed suitable in vivo model for monitoring PAHs exposure to hematopoietic tissue and other organs.
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsimri, Hwasun-eup, Hwasun-gun, Jeollanam-do 519-809, Republic of Korea ; Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Hwan-Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, Republic of Korea ; Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsimri, Hwasun-eup, Hwasun-gun, Jeollanam-do 519-809, Republic of Korea.
authors.forename: Min-Gu
authors.identifier: 0000-0003-4946-8512
authors.initials: MG
authors.lastname: Kang
authors.affiliation: Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Nguyen Thi Dai
authors.initials: NT
authors.lastname: Trang
authors.affiliation: Environment Health Center for Childhood Leukemia and Cancer, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Hee-Jo
authors.initials: HJ
authors.lastname: Baek
authors.affiliation: Environment Health Center for Childhood Leukemia and Cancer, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Jae-Dong
authors.initials: JD
authors.lastname: Moon
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsimri, Hwasun-eup, Hwasun-gun, Jeollanam-do 519-809, Republic of Korea.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsimri, Hwasun-eup, Hwasun-gun, Jeollanam-do 519-809, Republic of Korea.
authors.forename: Soon-Pal
authors.initials: SP
authors.lastname: Suh
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsimri, Hwasun-eup, Hwasun-gun, Jeollanam-do 519-809, Republic of Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Ryang
authors.affiliation: Environment Health Center for Childhood Leukemia and Cancer, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Hoon
authors.initials: H
authors.lastname: Kook
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 160 Ilsimri, Hwasun-eup, Hwasun-gun, Jeollanam-do 519-809, Republic of Korea ; Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, Republic of Korea ; Environment Health Center for Childhood Leukemia and Cancer, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Myung-Geun
authors.initials: MG
authors.lastname: Shin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis* / Q000378:metabolism; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056915:DNA Copy Number Variations / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects*; D004625:Embryo, Nonmammalian; D006801:Humans; D034882:Lamins / Q000032:analysis* / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis* / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial; D034882:Lamins; D011084:Polycyclic Aromatic Hydrocarbons; D011065:Poly(ADP-ribose) Polymerases