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.

Relationship between ambient air pollution and DNA damage in Polish mothers and newborns.

“…Consistent with our findings, previous studies of adult populations have seen significant associations between active smoking and WBC PAH-DNA adduct levels (16,49,50), although results have not been consistent (51). Several prior studies using the 32P-postlabeling method, which measures a broad spectrum of adducts bound to DNA, have seen an association between maternal smoking and adduct levels in fetal samples (52)(53)(54). However, studies using methodologies specific to PAH-DNA adducts have not (52,55,56).…”

Biomarker studies in northern Bohemia.

“…Biomarkers of human exposure, dose, and genetic effects in the general population have recently been studied with respect to exposures from environmental pollution (5)(6)(7)11,13,(28)(29)(30)(31)(32). Perera et al (5) found that the exposure to environmental pollution in the Silesian region of Poland was associated with a significant increase of DNA adducts, SCE, and CA, as well as with a frequency of ras oncogene overexpression.…”

Polychlorinated biphenyls (PCBs) as initiating agents in hepatocellular carcinoma

“…Thus Gallagher and coworkers did not see elevated DNA adduct levels in the placentas of non-smoking Taiwanese women who had been exposed to PCBs and polychlorinated dibenzofurans compared to non (less)-exposed non-smoking women from Taiwan or the USA [27]. They also measured arylhydrocarbon hydroxylase (AHH) activity in these tissues and found similar levels in placentas from American smokers and Taiwanese PCB-exposed non-smokers, but higher DNA adduct levels only in the American smoker samples, indicating that AHH induction alone is not sufficient to increase DNA adduct levels.…”