TY - JOUR
T1 - Gene expression profiles in the brain of the neonate mouse perinatally exposed to methylmercury and/or polychlorinated biphenyls
AU - Shimada, Miyuki
AU - Kameo, Satomi
AU - Sugawara, Norio
AU - Yaginuma-Sakurai, Kozue
AU - Kurokawa, Naoyuki
AU - Mizukami-Murata, Satomi
AU - Nakai, Kunihiko
AU - Iwahashi, Hitoshi
AU - Satoh, Hiroshi
PY - 2010/4
Y1 - 2010/4
N2 - 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 × 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.
AB - 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 × 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.
KW - Aroclor 1254
KW - Brain
KW - Co-exposure
KW - Gene expression
KW - Methylmercury
KW - Microarray
KW - Mouse
KW - PCBs
KW - Polychlorinated biphenyls
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U2 - 10.1007/s00204-009-0493-0
DO - 10.1007/s00204-009-0493-0
M3 - Article
C2 - 20020106
AN - SCOPUS:77950467100
VL - 84
SP - 271
EP - 286
JO - Archiv fur Toxikologie
JF - Archiv fur Toxikologie
SN - 0003-9446
IS - 4
ER -