COMPARISON OF DNA ADDUCT LEVELS IN HUMAN PLACENTA FROM POLYCHLORINATED BIPHENYL EXPOSED WOMEN AND SMOKERS IN WHICH CYP 1A1 LEVELS ARE SIMILARLY ELEVATED

Previous studies demonstrated that cigarette smoking is associated wit h high elevations in levels of both cytochrome P450 1A1 (CYP 1A1) acid DNA adducts in human placenta. To date, the identity of the smoking r elated DNA adducts is not known. The DNA adducts identified in placent a of smokers could result from chemicals present in cigarette smoke, s ubstances formed by CYP 1A1 metabolic activation of endogenous compoun ds, non-cigarette related exposures or a combination of these processe s. Exposure to contaminated rice oil containing large doses of polychl orinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) al so resulted in massive elevation of CYP 1A1 in human placenta but form ation of DNA adducts directly from this exposure has not previously be en reported. The purpose for comparing the two populations was to test the hypothesis that if CYP 1A1 induction results in the metabolic act ivation of endogenous compounds, then DNA adducts should also be prese nt in PCB/PCDF exposed tissues exhibiting high CYP 1A1 activity and so me of the adducts detected in the placental DNA from smokers may be id entified as those derived from the metabolic activation of endogenous compounds. To test this hypothesis, we measured DNA adducts using P-32 -postlabeling to analyze placental DNA from women exposed to PCB/PCDF and from cigarette smokers where levels of CYP 1A1 were similarly elev ated. There was no evidence of DNA adducts among specimens obtained fr om PCB/PCDF exposed individuals. These data suggest that CYP 1A1 induc tion alone (in the absence of cigarette smoking) does not induce the f ormation of DNA adducts detectable by this approach, and that smoking related adducts are not a consequence of CYP 1A1 induction mediated ac tivation of endogenous compounds or xenobiotics other than cigarette s moke. (C) 1994 Wiley-Liss, Inc.