Dataset Information

Clearance of polychlorinated biphenyl atropisomers is enantioselective in female C57Bl/6 mice.

ABSTRACT: Changes in the enantiomeric composition of polychlorinated biphenyls (PCBs) can not only be used to investigate environmental and biological transport processes, but also have human health implications because of enantiospecific adverse health effects. To further understand differences in the disposition of PCB atropisomers in vivo, the present study investigates the toxicokinetics of PCB atropisomers in female C57Bl/6 mice after oral administration of a mixture of several PCBs, including racemic PCBs 91, 95, 132, 136, 149, 174, and 176. On the Chirasil-Dex column, an enrichment of the second eluting atropisomers was generally observed, whereas only the first eluting atropisomers E1-PCB 95, (-)-PCB 132, and (-)-PCB 149 had half-lives that were distinctively longer compared to the second eluting atropisomers. The bioavailability normalized clearance of first eluting atropisomers in blood was faster compared to that of second eluting atropisomers. The opposite trend was observed for the accumulation factors in adipose tissue, which is consistent with the slower clearance of the first eluting atropisomer. The only exception was PCB 174, which showed no differences in the toxicokinetic parameters of both atropisomers. Together, the differences in the toxicokinetics of PCB atropisomers point toward enantioselective biotransformation processes as the origin of PCB's enantiomeric enrichment in mammals and, possibly, humans.

SUBMITTER: Kania-Korwel I

PROVIDER: S-EPMC2855138 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Clearance of polychlorinated biphenyl atropisomers is enantioselective in female C57Bl/6 mice.

Kania-Korwel Izabela I El-Komy Mohammed H M E MH Veng-Pedersen Peter P Lehmler Hans-Joachim HJ

Environmental science & technology 20100401 8

Changes in the enantiomeric composition of polychlorinated biphenyls (PCBs) can not only be used to investigate environmental and biological transport processes, but also have human health implications because of enantiospecific adverse health effects. To further understand differences in the disposition of PCB atropisomers in vivo, the present study investigates the toxicokinetics of PCB atropisomers in female C57Bl/6 mice after oral administration of a mixture of several PCBs, including racemi ...[more]

PMID: 20384376

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Project description:We analyzed the transcriptional response of the actinomycete Rhodococcus aetherivorans I24 to biphenyl and polychlorinated biphenyls (PCBs). This species has not been extensively exposed to PCBs, as it was first isolated from a toluene contaminated aquifer, rather than a site contaminated with polychlorinated hydrocarbons. Using a microarray targeting 3524 genes, we assessed gene expression in minimal medium supplemented with various substrates (e.g. PCBs) and in both PCB-contaminated and non-contaminated sediment slurries. Relative to the reference condition (minimal medium supplemented with glucose), 408 genes were up-regulated in the various treatments. In medium and in sediment, PCBs elicited the up-regulation of a common set of 100 genes, including chaperones (groEL), a superoxide dismutase (sodA), alkyl hydroperoxide reductase protein C (ahpC), and a catalase/peroxidase (katG). Analysis of the R. aetherivorans I24 genome sequence identified orthologs of many of the genes in the canonical biphenyl pathway, but very few of these genes were up-regulated in response to PCBs or biphenyl. This study is one of the first which utilizes microarrays to assess the transcriptional response of a soil bacterium to a pollutant under conditions which more closely resemble the natural environment. Our results indicate that the transcriptional response of R. aetherivorans I24 to PCBs, in both medium and sediment, is primarily directed towards reducing oxidative stress, rather than catabolism. In addition, the identification of numerous genes expressed in contaminated soil specifically may have implications for the development of biosensors. Finally, comparative genomic and transcriptomic analyses suggest that the mere presence of orthologs of the required enzymes may not be sufficient to confer a vigorous biphenyl/PCB metabolism. RNA was isolated from cells incubated in the following: sediment from a PCB-contaminated industrial site, uncontaminated sediment from a comparable site, and defined media supplemented with glucose (3 g/L), glucose and biphenyl (3 g/L, 4.5 Î¼M), or glucose and PCBs (3 g/L, 5 mg/L Aroclor 1254). In all cases, there were 3 biological replicates and 2 technical replicates (repeat hybridizations). A total of 3524 genes are represented on the arrays; of these, 41 and 176 are found on the plasmids pRA2 and pRA3, respectively. On average, there are 3 distinct 24nt probes per gene.

Dataset Information

Clearance of polychlorinated biphenyl atropisomers is enantioselective in female C57Bl/6 mice.

Publications

Clearance of polychlorinated biphenyl atropisomers is enantioselective in female C57Bl/6 mice.

Similar Datasets

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