title: Comparison of DNA adduct levels in human placenta from polychlorinated biphenyl exposed women and smokers in which CYP 1A1 levels are similarly elevated.
abstract: Previous studies demonstrated that cigarette smoking is associated with high elevations in levels of both cytochrome P450 1A1 (CYP1A1) and DNA adducts in human placenta. To date, the identity of the smoking related DNA adducts is not known. The DNA adducts identified in placenta of smokers could result from chemicals present in cigarette smoke, substances formed by CYP 1A1 metabolic activation of endogenous compounds, noncigarette related exposures or a combination of these processes. Exposure to contaminated rice oil containing large doses of polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) also resulted in massive elevation of CYP 1A1 in human placenta but formation of DNA adducts directly from this exposure has not previously been reported. The purpose for comparing the two populations was to test the hypothesis that if CYP 1A1 induction results in the metabolic activation of endogenous compounds, then DNA adducts should also be present in PCB/PCDF exposed tissues exhibiting high CYP 1A1 activity and some of the adducts detected in the placental DNA from smokers may be identified as those derived from the metabolic activation of endogenous compounds. To test this hypothesis, we measured DNA adducts using 32P-postlabeling to analyze placental DNA from women exposed to PCB/PCDF and from cigarette smokers where levels of CYP 1A1 were similarly elevated. There was no evidence of DNA adducts among specimens obtained from PCB/PCDF exposed individuals. These data suggest that CYP 1A1 induction alone (in the absence of cigarette smoking) does not induce the formation of DNA adducts detectable by this approach, and that smoking related adducts are not a consequence of CYP 1A1 induction mediated activation of endogenous compounds or xenobiotics other than cigarette smoke.
authors.affiliation: Health Effects Research Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
authors.forename: J E
authors.initials: JE
authors.lastname: Gallagher
authors.forename: R B
authors.initials: RB
authors.lastname: Everson
authors.forename: J
authors.initials: J
authors.lastname: Lewtas
authors.forename: M
authors.initials: M
authors.lastname: George
authors.forename: G W
authors.initials: GW
authors.lastname: Lucier
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001572:Benzofurans / Q000378:metabolism / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004247:DNA / Q000378:metabolism*; D000072338:Dibenzofurans, Polychlorinated; D004781:Environmental Exposure; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D010920:Placenta / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D011247:Pregnancy; D012907:Smoking / Q000378:metabolism*
chemical_list: D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D007527:Isoenzymes; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases