title: In vitro and in vivo induction of cytochrome P450 by coplanar polychlorinated/brominated biphenyls (Co-PXBs) providing high TEQ in mother's milk in Japan.
abstract: Coplanar polychlorinated/brominated biphenyls (Co-PXBs) are environmental pollutants previously identified in market fish samples. In this study, we observed that mother's milk in Japan is contaminated with Co-PXBs. Based on assumption that the toxicity of the same congener of PXDDs/DFs and Co-PXBs is nearly equal to that of the corresponding PCDDs/DFs and Co-PCBs, respectively, the toxic equivalent (TEQ) concentration was 10% of the total TEQ concentration (∑PCDDs/DFs, ∑PXDDs/DFs, ∑Co-PCBs and ∑Co-PXBs) in the milk. This observation suggested that humans, and especially infants, are exposed to high levels of Co-PXBs, which might cause adverse effects. However, the toxicity of Co-PXBs has to date not been reported. We assessed the toxic potency of Co-PXBs by studying their effect on the activity of cytochrome P450. Only the mRNA level and activity of CYP1A increased in a dose-dependent manner upon exposure to Co-PXBs. Substitution of bromine for chlorine into Co-PCBs provided higher CYP1A activity in in vitro and in vivo experiments. The expression level of aryl hydrocarbon receptor (AhR) mRNA was not altered, but luciferase activity, an indicator of AhR transcriptional activity, increased following treatment with Co-PXBs. The results suggest that CYP1A induction by Co-PXBs depended on AhR transcriptional activity and not on AhR expression. Although the TEFs of Co-PXBs are not set, if Co-PXBs are included in these calculations because of their higher toxicity compared to Co-PCBs, exposure to Co-PXBs cannot be neglected when assessing human health risks.
authors: Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101, Japan.
authors: Hideki
authors: H
authors: Kakutani
authors: Department of Life Science, Faculty of Science and Engineering, Setsunan University, Osaka 573-0101, Japan.
authors: Osamu
authors: O
authors: Aozasa
authors: Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101, Japan.
authors: Ayami
authors: A
authors: Mizuno
authors: Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101, Japan.
authors: Ema
authors: E
authors: Akiyama
authors: Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101, Japan.
authors: Teruyuki
authors: T
authors: Nakao
authors: Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101, Japan. Electronic address: ohta@pharm.setsunan.ac.jp.
authors: Souichi
authors: S
authors: Ohta
mesh_terms: D000328:Adult; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects / Q000378:metabolism; D061186:Breast Milk Expression; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D004790:Enzyme Induction; D005260:Female; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007564:Japan; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008895:Milk, Human / Q000378:metabolism*; D011075:Polybrominated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism; D018570:Risk Assessment; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019363:Cytochrome P-450 CYP1A1; D004785:Environmental Pollutants; D011075:Polybrominated Biphenyls; D011078:Polychlorinated Biphenyls; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human; C484722:Ahr protein, mouse; C569463:CYP1A1 protein, human
keywords: 7-ethoxyresorufin-O-deethoxyrase activity; Aryl hydrocarbon receptor; Coplanar polychlorinated/brominated biphenyls