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H2AX phosphorylation in A549 cells induced by the bulky and stable DNA adducts of benzo[a]pyrene and dibenzo[a,l]pyrene diol epoxides
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2009 (English)In: Chemico-Biological Interactions, ISSN 0009-2797, E-ISSN 1872-7786, Vol. 177, no 1, 40-47 p.Article in journal (Refereed) Published
Abstract [en]

Early events in the cellular response to DNA damage, such as double strand breaks, rely on lesion recognition and activation of proteins involved in maintenance of genomic stability. One important component of this process is the phosphorylation of the histone variant H2AX. To investigate factors explaining the variation in carcinogenic potency between different categories of polycyclic aromatic hydrocarbons (PAHs). we have studied the phosphorylation of H2AX (H2AX gamma). A549 cells were exposed to benzo[a]pyrene diol epoxide [(+)-anti-BPDE] (a bay-region PAH) and dibenzo[a,l]pyrene diol epoxide [(-)-anti-DBPDE] (a fjord-region PAH) and H2AX gamma was studied using immunocytochemistry and Western blot. Hydrogen peroxide (H2O2) was used to induce oxidative DNA damage and strand breaks. As showed with single cell gel electrophoresis, neither of the diol epoxides resulted in DNA strand breaks relative to H2O2. Visualisation of H(2)AX gamma formation demonstrated that the proportion of cells exhibiting H2AX gamma staining at 1 h differed between BPDE, 40% followed by a decline, and DBPDE, <10% followed by an increase. With H2O2 treatment, almost all cells demonstrated H(2)AX gamma at 1 h. Western blot analysis of the H2AX gamma formation also showed concentration and time-dependent response patterns. The kinetics of H2AX gamma formation correlated with the previously observed kinetics of elimination of BPDE and DBPDE adducts. Thus, the extent of H2AX gamma formation and persistence was related to both the number of adducts and their structural features.

Place, publisher, year, edition, pages
2009. Vol. 177, no 1, 40-47 p.
Keyword [en]
PAH, Diol epoxide, BPDE, DBPDE, DNA adducts, H2AX
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-137376DOI: 10.1016/j.cbi.2008.09.015ISI: 000262603700007OAI: oai:DiVA.org:uu-137376DiVA: diva2:378229
Available from: 2010-12-15 Created: 2010-12-15 Last updated: 2010-12-15Bibliographically approved

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