scholarly journals Mammalian Cytochrome P450-Dependent Metabolism of Polychlorinated Dibenzo-p-dioxins and Coplanar Polychlorinated Biphenyls

2014 ◽  
Vol 15 (8) ◽  
pp. 14044-14057 ◽  
Author(s):  
Hideyuki Inui ◽  
Toshimasa Itoh ◽  
Keiko Yamamoto ◽  
Shin-Ichi Ikushiro ◽  
Toshiyuki Sakaki
2020 ◽  
Author(s):  
Xueshu Li ◽  
Chun-Yun Zhang ◽  
Hans-Joachim Lehmler

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that are linked to adverse health outcomes. PCB tissue levels are determinants of PCB toxicity; however, it is unclear how factors, such as an altered metabolism and/or a fatty liver, affect PCB distribution in vivo. We determined the congener-specific disposition of PCBs in mice with a liver specific deletion of cytochrome P450 reductase (KO), a model of fatty liver with impaired hepatic metabolism, and wildtype (WT) mice. Male and female KO and WT mice were exposed orally to Aroclor 1254, a technical PCB mixture. PCBs were quantified in adipose, blood, brain and liver tissues by gas chromatography-mass spectrometry. PCB profiles and levels in tissues were genotype and sex dependent. PCB levels were higher in the liver from KO compared to WT mice. PCB profiles showed clear differences between tissues from the same exposure group. While experimental tissue : blood partition coefficients in KO and WT mice did not follow the trends predicted using a composition-based model, the agreement between experimental and calculated partition coefficients was still reasonable. Thus, a fatty liver and/or an impaired hepatic metabolism alter the distribution of PCBs in mice and the magnitude of the partitioning of PCBs from blood into tissues can be approximated using composition-based models.<br>


2013 ◽  
Vol 47 (21) ◽  
pp. 12184-12192 ◽  
Author(s):  
Zhe Lu ◽  
Izabela Kania-Korwel ◽  
Hans-Joachim Lehmler ◽  
Charles S. Wong

2010 ◽  
Vol 675 (2) ◽  
pp. 138-147 ◽  
Author(s):  
Miriam Altstein ◽  
Orna Ben Aziz ◽  
Nir Skalka ◽  
Alisa Bronshtein ◽  
Jane C. Chuang ◽  
...  

1995 ◽  
Vol 3 (2) ◽  
pp. 171-190 ◽  
Author(s):  
Christopher D. Metcalfe ◽  
G. Douglas Haffner

Polychlorinated biphenyls (PCBs) have been recognized for over 25 years as global environmental contaminants. However, many PCB congeners may be relatively harmless, while a small group of PCB congeners are highly toxic to biota. The toxic coplanar PCB congeners are chlorinated at meta positions and at one or none of the ortho positions on the biphenyl ring, thus resembling 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in molecular configuration. In vitro and in vivo toxicity tests with rodents, fish, and birds have shown that the coplanar PCB congener 126 is almost as toxic as TCDD. Several coplanar PCBs (e.g., 77, 126, 105, 118) are present in biota at parts per billion concentrations, which is orders of magnitude higher than concentrations of TCDD. Thus, coplanar PCBs may account for over 95% of the dioxinlike toxic activity affecting biota, such as fish-eating birds in the Great Lakes. There is some evidence that the toxicokinetics of coplanar PCBs in organisms differs from that of other PCB homologues. If coplanar PCBs are more persistent than their homologues, they could become enriched in biota as they pass up through the food chain (i.e., trophic enrichment), or as overall PCB levels decline with time (i.e., temporal enrichment). Overall, the available data do not support the concept of trophic or temporal enrichment in the environment.Key words: polychlorinated biphenyls, coplanar, toxic equivalents, kinetics, mixed function oxidase, 7-ethoxyresorufin-O-deethylase.


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