title: 2,3,7,8-Tetrachlorodibenzo-p-dioxin modulates estradiol-induced aldehydic DNA lesions in human breast cancer cells through alteration of CYP1A1 and CYP1B1 expression.
abstract: BACKGROUND
  Many genes responsible for the bioactivation of endogenous estrogen to reactive quinonoid metabolites, including cytochrome P450 (CYP) 1A1, 1A2, and 1B1, are well-known target genes of the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
  
  
  METHODS
  The purpose of this research was to investigate the roles of TCDD-mediated altered gene expression in the induction of aldehydic DNA lesions (ADLs) by 17β-estradiol (E2) in human MDA-MB-231 and MCF-7 breast cancer cells.
  
  
  RESULTS
  We demonstrated that increases in the number of oxidant-mediated ADLs, including abasic sites and aldehydic base/sugar lesions, were detected in MDA-MB-231 cells exposed to E2. The DNA-damaging effects of E2 in MDA-MB-231 cells were prevented by pretreatment of cells with TCDD. In contrast, we did not observe statistically significant increases in the number of ADLs in MCF-7 cells exposed to E2. However, with TCDD pretreatment, an approximately twofold increase in the number of ADLs was detected in MCF-7 cells exposed to E2.
  
  
  CONCLUSIONS
  TCDD pretreatment induces disparity in the disposition of E2 to reactive quinonoid metabolites and the subsequent formation of oxidative DNA lesions through alteration of CYP1A1 and CYP1B1 expression in human breast cancer cells.
authors.affiliation: Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Shou-Tung
authors.initials: ST
authors.lastname: Chen
authors.forename: Dar-Ren
authors.initials: DR
authors.lastname: Chen
authors.forename: Ju-Pin
authors.initials: JP
authors.lastname: Fang
authors.forename: Po-Hsiung
authors.initials: PH
authors.lastname: Lin
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D020552:Comet Assay; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D004785:Environmental Pollutants / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000447:Aldehydes; D004785:Environmental Pollutants; D004967:Estrogens; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D004958:Estradiol; D004247:DNA; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1