PMID- 14737002
OWN - NLM
STAT- MEDLINE
DCOM- 20050506
LR  - 20171116
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 78
IP  - 2
DP  - 2004 Apr
TI  - 2,2',4,6,6'-Pentachlorobiphenyl induces mitotic arrest and p53 activation.
PG  - 215-21
AB  - 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.
FAU - Shin, Kum-Joo
AU  - Shin KJ
AD  - 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.
FAU - Kim, Sun-Hee
AU  - Kim SH
FAU - Kim, Dohan
AU  - Kim D
FAU - Kim, Yun-Hee
AU  - Kim YH
FAU - Lee, Han-Woong
AU  - Lee HW
FAU - Chang, Yoon-Seok
AU  - Chang YS
FAU - Gu, Man-Bock
AU  - Gu MB
FAU - Ryu, Sung Ho
AU  - Ryu SH
FAU - Suh, Pann-Ghill
AU  - Suh PG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040121
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Environmental Pollutants)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
RN  - Z4YYF101N3 (2,2',4,6,6'-pentachlorobiphenyl)
SB  - IM
MH  - Animals
MH  - CDC2 Protein Kinase
MH  - Comet Assay
MH  - Environmental Pollutants/*toxicity
MH  - Luciferases
MH  - Mice
MH  - Mitosis/*drug effects
MH  - NIH 3T3 Cells
MH  - Polychlorinated Biphenyls/*toxicity
MH  - *Polyploidy
MH  - Spindle Apparatus/drug effects
MH  - Tumor Suppressor Protein p53/deficiency/genetics/*metabolism
EDAT- 2004/01/23 05:00
MHDA- 2005/05/07 09:00
CRDT- 2004/01/23 05:00
PHST- 2004/01/23 05:00 [pubmed]
PHST- 2005/05/07 09:00 [medline]
PHST- 2004/01/23 05:00 [entrez]
AID - kfh069 [pii]
AID - 10.1093/toxsci/kfh069 [doi]
PST - ppublish
SO  - Toxicol Sci. 2004 Apr;78(2):215-21. doi: 10.1093/toxsci/kfh069. Epub 2004 Jan 21.