Benzo[a]pyrene-induced cell cycle arrest in HepG2 cells is associated with delayed induction of mitotic instability

Mutation Research
Dimitris StellasSoterios A Kyrtopoulos

Abstract

The environmental carcinogen benzo[a]pyrene (B[a]P) after being metabolised by cytochrome P450 enzymes forms DNA adducts. This abnormal situation induces changes in the cell cycle, DNA damage, chromosomal and mitotic aberrations, all of which may be related to carcinogenesis. In order to further investigate the mechanistic basis of these effects, HepG2 cells were treated with 3μM B[a]P for various time periods, followed by further incubation in the absence of B[a]P for up to 192h. B[a]P treatment led initially to S-phase arrest followed by recovery and subsequent induction of G2/M arrest, indicating activation of the corresponding DNA damage checkpoints. Immunofluorescence-based studies revealed accumulation of B[a]P-induced DNA adducts and chromosomal damage which persisted beyond mitosis and entry into a new cycle, thus giving rise to a new round of activation of the S-phase checkpoint. Prolonged further cultivation of the cells in the absence of B[a]P resulted in high frequencies of various abnormal mitotic events. Abrogation of the B[a]P-induced S-phase arrest by the Chk1 inhibitor UCN-01 triggered a strong apoptotic response but also dramatically decreased the frequency of mitotic abnormalities in the surviving cells, sugg...Continue Reading

References

Sep 1, 1992·Genes & Development·C B Epstein, F R Cross
Jan 31, 1997·The Journal of Biological Chemistry·C Vaziri, D V Faller
Jan 15, 2000·The Journal of Biological Chemistry·N GuoC Vaziri
Feb 24, 2001·Neoplasia : an International Journal for Oncology Research·B D JeffyD F Romagnolo
Sep 7, 2001·Genes & Development·R T Abraham
Jun 13, 2002·Environmental Health Perspectives·Carl-Elis BoströmRoger Westerholm
Oct 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Hui ZhaoHelen Piwnica-Worms
Jan 17, 2003·Molecular and Cellular Biology·Robert S WeissCyrus Vaziri
Mar 12, 2003·Genes & Development·Eric J Brown, David Baltimore
Aug 18, 2004·Nature Cell Biology·Alwin KrämerJiri Lukas
Jan 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Xingxu HuangPumin Zhang
Jan 25, 2005·Nature Cell Biology·Claus Storgaard SørensenThomas Helleday
Feb 16, 2005·Cancer Cell·Janusz PucRamon Parsons
Oct 6, 2005·Cancer Research·Baocheng HuYa Wang
Apr 4, 2006·Molecular and Cellular Biology·Eva PetermannKeith W Caldecott
May 25, 2006·Cell Cycle·Veronique A J Smits
Jul 21, 2006·Experimental Cell Research·Harald LöfflerAlwin Krämer
Jul 29, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jiabin TangXiaoqi Liu
Aug 17, 2006·The Journal of Biological Chemistry·Peijun LiuCyrus Vaziri
Feb 6, 2007·Developmental Cell·George ZachosDavid A F Gillespie
Feb 22, 2007·Cell Cycle·Paula J Hurley, Fred Bunz
Mar 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dimitris StellasEvangelia Patsavoudi
May 1, 2007·EMBO Reports·Emer BourkeCiaran G Morrison
May 12, 2007·The EMBO Journal·Apolinar Maya-MendozaDean A Jackson
Jul 12, 2008·Biochemical and Biophysical Research Communications·Hiromichi NaruyamaMakoto Nakanishi
Dec 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Deborah WilskerFred Bunz
Oct 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Aniek JanssenRené H Medema
Jul 14, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Joost H M van DelftJos C S Kleinjans
Apr 30, 2011·Nature Reviews. Molecular Cell Biology·Ilio VitaleGuido Kroemer
Dec 12, 2012·The Journal of Cell Biology·Neil J Ganem, David Pellman

❮ Previous
Next ❯

Citations

May 26, 2017·Journal of Medicinal Food·Liliane Menezes FernandesVeronica Elisa Pimenta Vicentini
Jul 13, 2018·Journal of Toxicology and Environmental Health. Part a·Katiuska TuttisIlce Mara de Syllos Cólus
Feb 13, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Saleh A AlmatroodiArshad Husain Rahmani

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.