Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Benzo[a]pyrene-induced cell cycle arrest in HepG2 cells is associated with delayed induction of mitotic instability
Δημιουργός/Συγγραφέας:	[EL] Στέλλας, Δημήτρης[EN] Stellas, Dimitris [EL] Σουλιώτης, Βασίλης Λ.[EN] Souliotis, Vassilis L. [EL] Μπεκύρου, Μαργαρίτα[EN] Bekyrou, Margarita Smirlis D. Kirsch-Volders M. Degrassi F. Cundari E. [EL] Κυρτόπουλος, Σωτήριος Α.[EN] Kyrtopoulos, Soterios A.
Εκδότης:	Elsevier B.V.
Ημερομηνία:	2014
Γλώσσα:	Αγγλικά
ISSN:	0027-5107
DOI:	10.1016/j.mrfmmm.2014.07.004
Άλλο:	PubMed ID: 25771725
Περίληψη:	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 3. μM B[a]P for various time periods, followed by further incubation in the absence of B[a]P for up to 192. h. 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, suggesting that events occurring during S-phase arrest contribute to the formation of delayed mitotic damage. Overall, our data demonstrate that, although S-phase arrest serves as a mechanism by which the cells reduce their load of genetic damage, its prolonged activation may also have a negative impact on the balance between cell death and heritable genetic damage.
Τίτλος πηγής δημοσίευσης:	Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Τόμος/Κεφάλαιο:	769
Σελίδες:	59-68
Θεματική Κατηγορία:	[EL] Περιβαλλοντική υγεία[EN] Environmental health
Λέξεις-Κλειδιά:	Benzo[a]pyrene Carcinogenesis Chk1 Mitotic abnormalities S-phase arrest
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2014 Elsevier B.V.
Σημειώσεις:	This work was supported by the European project ECNIS ( Environmental Cancer Risk, Nutrition and Individual Susceptibility ). FOOD-CT-2005-513943
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο