10.1021/tx700252n.s003 Sarah L. Hockley Sarah L. Hockley Volker M. Arlt Volker M. Arlt Daniel Brewer Daniel Brewer Robert te Poele Robert te Poele Paul Workman Paul Workman Ian Giddings Ian Giddings David H. Phillips David H. Phillips AHR- and DNA-Damage-Mediated Gene Expression Responses Induced by Benzo(<i>a</i>)pyrene in Human Cell Lines American Chemical Society 2007 Human Cell LinesCarcinogens NQO aryl hydrocarbon receptor BPDE BaP AHR MAK cell lines cell cycle regulation TCDD gene expression profiles 29 expression changes 1B HepG 2 cells DNA damage DNA damage response CYP 78 expression changes MGST MCF 2007-12-17 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/AHR_and_DNA_Damage_Mediated_Gene_Expression_Responses_Induced_by_Benzo_i_a_i_pyrene_in_Human_Cell_Lines/2968684 Carcinogens induce complex transcriptional responses in cells that may hold key mechanistic information. Benzo(<i>a</i>)pyrene (BaP) modulation of transcription may occur through the activation of the aryl hydrocarbon receptor (AHR) or through responses to DNA damage. To characterize further the expression profiles induced by BaP in HepG2 and MCF-7 cells obtained in our previous study, they were compared to those induced by 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD), which activates AHR but does not bind to DNA, and <i>anti</i>-benzo(<i>a</i>)pyrene-<i>trans</i>-7,8-dihydrodiol-9,10-epoxide (BPDE), which binds directly to DNA but does not activate AHR. A total of 22 genes had altered expression in MCF-7 cells after both BaP and TCDD exposure, and a total of 29 genes had altered expression in HepG2 cells. In both cell lines, xenobiotic metabolism was upregulated through induction of <i>NQO1</i>, <i>MGST1</i>, and <i>CYP1B1</i>. A total of 78 expression changes were induced by both BaP and BPDE in MCF-7 cells, and a total of 29 expression changes were induced by both BaP and BPDE in HepG2 cells. These genes were predominantly involved in cell cycle regulation, apoptosis, and DNA repair. BaP and BPDE caused the repression of histone genes in both cell lines, suggesting that regulation of these genes is an important component of the DNA damage response. Interestingly, overlap of the BPDE and TCDD gene expression profiles was also observed. Furthermore, some genes were modulated by BaP but not by TCDD or BPDE, including induction of <i>CRY1</i> and <i>MAK</i>, which may represent novel signaling pathways that are independent of both AHR activation and DNA damage. Promoter analysis identified candidate genes for direct transcriptional regulation by either AHR or p53. These analyses have further dissected and characterized the complex cellular response to BaP.