2,2′,4,6,6′-Pentachlorobiphenyl induces mitotic arrest and p53 activation

Kum Joo Shin, Sun Hee Kim, Dohan Kim, Yun Hee Kim, Han Woong Lee, Yoon Seok Chang, Man Bock Gu, Sung Ho Ryu, Pann Ghill Suh

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3 Citations (Scopus)

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′-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.

Original languageEnglish
Pages (from-to)215-221
Number of pages7
JournalToxicological Sciences
Volume78
Issue number2
DOIs
Publication statusPublished - 2004 Apr 1

All Science Journal Classification (ASJC) codes

  • Toxicology

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    Shin, K. J., Kim, S. H., Kim, D., Kim, Y. H., Lee, H. W., Chang, Y. S., Gu, M. B., Ryu, S. H., & Suh, P. G. (2004). 2,2′,4,6,6′-Pentachlorobiphenyl induces mitotic arrest and p53 activation. Toxicological Sciences, 78(2), 215-221. https://doi.org/10.1093/toxsci/kfh069