title: Gene expression profiles in the brain of the neonate mouse perinatally exposed to methylmercury and/or polychlorinated biphenyls.
abstract: Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are environmentally persistent neurodevelopmental toxicants. The primary source of human exposure is the consumption of contaminated fish, seafood and marine mammals. However, little is known about the molecular mechanisms of MeHg and PCB toxicities and interactions between these contaminants. We investigated the functional profiles of differently expressed genes in the brains of offspring mice perinatally exposed to MeHg and/or PCBs to elucidate how these contaminants interact with each other. Pregnant mice (C57BL/6) were divided into four groups by exposure: (1) vehicle control, (2) MeHg alone, (3) PCBs alone, (4) MeHg + PCBs. Gene expression analysis of the brains of offspring mice was carried out with 4 x 44 K whole mouse genome's microarrays (Agilent) on postnatal day 1. The gene expression pattern of the MeHg exposure-group differed from that of the PCB-exposure group. The MeHg + PCB group expressed a larger number of genes, most of which were not expressed in the MeHg group or PCB group. It was revealed that gene expression was greatly increased, and the most altered genes were found with co-exposure. The genes were related to the functional categories of development, inflammation, calcium ion homeostasis, signal transduction, the ubiquitin-proteasome pathway and detoxication. The ubiquitin-proteasome system and detoxication categories might function for protection against the toxicity induced by co-exposure to MeHg and PCBs. These results suggest that co-exposure does not simply exacerbate the toxicity of MeHg alone or PCB alone, but stimulates a protection system.
authors.affiliation: Department of Environmental Health Sciences, Tohoku University Graduate School of Medicine, 2-1 Seiryomachi, Aoba-ku, Sendai 980-8575, Japan. shimashima@ehs.med.tohoku.ac.jp
authors.forename: Miyuki
authors.initials: M
authors.lastname: Shimada
authors.forename: Satomi
authors.initials: S
authors.lastname: Kameo
authors.forename: Norio
authors.initials: N
authors.lastname: Sugawara
authors.forename: Kozue
authors.initials: K
authors.lastname: Yaginuma-Sakurai
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kurokawa
authors.forename: Satomi
authors.initials: S
authors.lastname: Mizukami-Murata
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nakai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Iwahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Satoh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D016000:Cluster Analysis; D004781:Environmental Exposure / Q000032:analysis; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy
chemical_list: D008767:Methylmercury Compounds; D011078:Polychlorinated Biphenyls