| Induction of the cell cycle regulatory gene p21 (Waf1, Cip1) following methylmercury exposure in vitro and in vivo. | |
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MedLine Citation:
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PMID: 10373404 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Methylmercury (MeHg) is recognized as a significant environmental hazard, particularly to the development of the nervous system. To study the molecular mechanisms underlying cell cycle inhibition by MeHg, we assessed the involvement of p21 (Waf1, Cip1), a cell cycle regulatory gene implicated in the G1 and G2 phases of cell cycle arrest, in primary embryonic cells and adult mice following MeHg exposure. Previous literature has supported the association of increased p21 expression with chondrocyte differentiation. In support of this finding, we observed an increasing p21 expression during limb bud (LB), but not midbrain central nervous system (CNS) cell differentiation. Both embryonic LB and CNS cells responded to MeHg exposure with a concentration-dependent increase in p21 mRNA. In the parallel adult study, C57BL/6 female mice were chronically exposed to 10 ppm MeHg via drinking water for 4 weeks. While there was limited or absent induction of Gadd45, Gadd153, and the gamma-glutamylcysteine synthetase catalytic subunit, p21 was markedly induced in the brain, kidney, and liver tissues in most of the animals that showed MeHg-induced behavioral toxicity such as hyperactivity and tremor. Furthermore, the induction of p21 mRNA was accompanied by an increase in p21 protein level. The results indicate that the activation of cell cycle regulatory genes may be one mechanism by which MeHg interferes with the cell cycle in adult and developing organisms. Continued examination of the molecular mechanisms underlying cell cycle inhibition may potentially lead to utilization of this mechanistic information to characterize the effects of MeHg exposure in vivo. |
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Authors:
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Y C Ou; S A Thompson; R A Ponce; J Schroeder; T J Kavanagh; E M Faustman |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 157 ISSN: 0041-008X ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 1999 Jun |
Date Detail:
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Created Date: 1999-07-12 Completed Date: 1999-07-12 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 203-12 Citation Subset: IM |
Copyright Information:
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Copyright 1999 Academic Press. |
Affiliation:
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Department of Environmental Health, University of Washington, Seattle, Washington 98195, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Northern Blotting, Western Cell Cycle / drug effects, genetics Cell Differentiation / drug effects Cell Survival / drug effects Cells, Cultured Cyclin-Dependent Kinase Inhibitor p21 Cyclins / genetics* Extremities / embryology Female Gene Expression Regulation* Mesencephalon / cytology, embryology Methylmercury Compounds / toxicity* Mice Mice, Inbred C57BL Organ Specificity Precipitin Tests Rats Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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5-P30-ES-07033/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cdkn1a protein, mouse; 0/Cdkn1a protein, rat; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Methylmercury Compounds; 1184-57-2/methylmercury hydroxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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