Abstract 2734: Ethanol potentiates tobacco smoke carcinogens-induced MAPK activation

Abstract

Abstract Alcohol consumption along with smoking is a well-known health hazard to human. How alcohol consumption potentiates the smoking mediated hazard is not clear. Previously we reported that DNA damage caused by tobacco smoke carcinogen (+/-) anti-benzo[a]pyrene-7, 8-diol-9,10-epoxide [BPDE] is responded by cells through induction of cell growth inhibition in different cell lines. Here we observed that ethanol (EtOH) treatment at physiologically relevant concentration (60mM) increases the DNA synthesis in DNA damaging carcinogen (BPDE) treated cells. BPDE treatment of cells elicits G1-S cell cycle arrest, but EtOH does not have any significant modulating effect of G1-S arrest, indicating increased DNA synthesis by EtOH is due to modulation of some other signaling event(s). We observed that EtOH co-treatment/ pretreatment potentiates BPDE induced phosphorylation and activation of extracellular regulated kinase 1/2 (ERK1/2). Interestingly, treatment of cells with MEK1 inhibitor (PD09059) significantly reduced EtOH's ability to increase DNA synthesis in BPDE treated cells. All together, these findings suggest that the ability of EtOH to potentiate BPDE-induced ERK activation may potentiates PAH-induced tumorigenesis. [Supported by NIH grant # R03 ES021779]. Citation Format: Manoj K. Pandey, Jagat J. Mukherjee, Dhimant H. Desai, Shantu G. Amin, Subodh Kumar. Ethanol potentiates tobacco smoke carcinogens-induced MAPK activation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2734. doi:10.1158/1538-7445.AM2015-2734