Skip Navigation


ToxSci Advance Access originally published online on January 21, 2004
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
78/2/215    most recent
kfh069v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Shin, K.-J.
Right arrow Articles by Suh, P.-G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shin, K.-J.
Right arrow Articles by Suh, P.-G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences 78, 215-221 (2004)
Toxicological Sciences vol. 78 no. 2 © Society of Toxicology; all rights reserved.

2,2',4,6,6'-Pentachlorobiphenyl Induces Mitotic Arrest and p53 Activation

Kum-Joo Shin*,{dagger}, Sun-Hee Kim*, Dohan Kim*, Yun-Hee Kim*, Han-Woong Lee{ddagger}, Yoon-Seok Chang§, Man-Bock Gu, Sung Ho Ryu* and Pann-Ghill Suh*,1

* Department of Life Science, Division of Molecular and Life Sciences, and School of Environmental Science and Engineering, Pohang University of Science and Technology, Pohang 790-784, Kyungbuk, Republic of Korea; § School of Environmental Science and Engineering, Pohang University of Science and Technology, Pohang 790-784, Kyungbuk, Republic of Korea; {dagger} Division of Biology, California Institute of Technology, Pasadena, California 91125, {ddagger} Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, Republic of Korea; and Kwangju Institute of Science and Technology, Oryong-dong, Puk-gu, Kwangju, Republic of Korea

Received November 28, 2003; accepted January 5, 2004

Polychlorinated biphenyls (PCBs), a class of persistent organic pollutants (POPs), have been considered to be involved in cancers, but the underlying mechanisms are not known well. Various cancers are closely related to genetic alteration; therefore, we investigated the effect of PCBs on genetic stability, through p53, a guardian of genome, in NIH 3T3 fibroblasts. Among several congeners examined, 2,2',4,6,6'-pentachlorobiphenyl (PeCB) specifically activated p53-dependent transcription. It also induced p53 nuclear accumulation, but did not cause DNA strand breakage. On the other hand, cell cycle progression that is closely connected to p53 was affected by 2,2',4,6,6'-PeCB, resulting in mitotic arrest. In the arrested cells, mitotic spindle damage was detected. Moreover, in the absence of functional p53, polyploidy was caused by 2,2',4,6,6'-PeCB. These results imply that 2,2',4,6,6'-PeCB induces mitotic arrest by interfering with mitotic spindle assembly, followed by genetic instability which triggers p53-activating signals to prevent further polyploidization. Taking these findings together, we suggest that 2,2',4,6,6'-PeCB could be involved in cancer development by causing genetic instability through mitotic spindle damage, which brings about aneuploidy in p53-deficient tumor cells.

Key Words: polychlorinated biphenyl; p53; mitotic arrest; genetic instability.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
S.-H. Kim, Y.-H. Kim, K.-J. Shin, Y.-S. Oh, C. S. Lee, K.-O. Kang, S. H. Ryu, and P.-G. Suh
2,2',4,6,6'-Pentachlorobiphenyl-Induced Apoptosis Is Limited by Cyclooxygenase-2 Induction
Toxicol. Sci., February 1, 2005; 83(2): 397 - 404.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.