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2,2 ',4,6,6 '-pentachlorobiphenyl induces mitotic arrest and p53 activation SCIE SCOPUS

Title
2,2 ',4,6,6 '-pentachlorobiphenyl induces mitotic arrest and p53 activation
Authors
Shin, KJKim, SHKim, DKirn, YHLee, HWChang, YSGu, MBRyu, SHSuh, PG
Date Issued
2004-04
Publisher
OXFORD UNIV PRESS
Abstract
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'-pentachlorobiphenyI (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 2,21,4,6,6'-PeCB could be involved in cancer development by causing genetic instability through mitotic spindle damage, which brings about aneuploidy in p53-deficient tumor cells.
Keywords
polychlorinated biphenyl; p53; mitotic arrest; genetic instability; POLYCHLORINATED-BIPHENYLS PCBS; AROCLOR 1254; OXIDATIVE STRESS; HORMONE LEVELS; LIVER-TUMORS; DNA-DAMAGE; IN-VIVO; INDUCTION; MITOSIS; MIXTURE
URI
https://oasis.postech.ac.kr/handle/2014.oak/17984
DOI
10.1093/toxsci/kfh069
ISSN
1096-6080
Article Type
Article
Citation
TOXICOLOGICAL SCIENCES, vol. 78, no. 2, page. 215 - 221, 2004-04
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장윤석CHANG, YOON-SEOK
Div of Environmental Science & Enginrg
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