| 3. |
- Nilsen, A.J., et al.
(author)
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Comparative hepatic gene expression profiling of rats treated with 1H,1H,2H,2H-heptadecafluorodecan-1-ol or with pentadecafluorooctanoic acid
- 2008
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In: Physiol. Genomics. - : American Physiological Society. ; 34, s. 285-303
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Journal article (peer-reviewed)abstract
- Pentadecafluorooctanoic acid is an established peroxisome proliferator. Little is known about effects of treatment with 1 H,1 H,2 H,2 H-heptadecafluorodecan-1-ol, which is metabolized to pentadecafluorooctanoic acid. We compared effects of various dosages (3, 10, or 25 mg/kg body wt) of each of these compounds on hepatic gene expression in rats with microarrays. Microarray data were validated by real-time RT-PCR. Expression data were also correlated with hepatic activities of selected enzymes and with hepatic levels of pentadecafluorooctanoic acid and 1 H,1 H,2 H,2 H-heptadecafluorodecan-1-ol. Pentadecafluorooctanoic acid caused the more powerful change in gene expression, in terms of both number of genes affected and extent of change in expression. Across the dosages used pentadecafluorooctanoic acid and 1 H,1 H,2 H,2 H-heptadecafluorodecan-1-ol caused significant ( P ≤ 0.05) changes in expression for 441 and 105 genes, respectively. With 1 H,1 H,2 H,2 H-heptadecafluorodecan-1-ol ∼38% of the 105 genes exhibited decreased expression with a dose of 25 mg/kg body wt, these genes also appearing less responsive to treatment at the lower dosages. Bioinformatic analysis suggested that these genes are associated with regulatory functions. With pentadecafluorooctanoic acid, increasing dosage up to 10 mg/kg body wt brought about progressive increase in expression of affected genes. Pathways analysis suggested similar effects of the two compounds on lipid and amino acid metabolism. Marked differences were also found, particularly with respect to effects on genes related to oxidative phosphorylation, oxidative metabolism, free radical scavenging, xenobiotic metabolism, and complement and coagulation cascades.
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| 4. |
- Voiea, Ø A, et al.
(author)
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Activation of Respiratory Burst in Human Granulocytes by Polychlorinated Biphenyls : A Structure–Activity Study
- 2000
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In: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X. ; 167:2, s. 118-24
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Journal article (peer-reviewed)abstract
- The respiratory burst in human granulocytes activated by 33 different congeners of polychlorinated biphenyls (PCBs) was measured as luminol-amplified chemoluminescence. The selection of 20 (training set) compounds was based on multivariate chemical characterization, laying the groundwork for covering the whole chemical series of tetra- through hepta-chlorinated PCBs. In addition 6 congeners were used as a validation set, and 7 were mono- to tri-chlorinated congeners representing low-chlorinated compounds not covered by the training set. Only ortho-substituted biphenyls activate respiratory burst. There is a correlation between activated respiratory burst and the total surface area of congeners up to 230 × 10−20 m2. Congeners of larger size show a reduced activity. There is also a correlation between respiratory burst activity and the number of ortho-substituents. Furthermore, there is also a correlation with parameters that describe absolute hardness of the molecule and respiratory burst activity. Congeners with a 2,4,6-substitution on one biphenyl ring are optimal activators. In conclusion, all three factors, size, rotation, and electronic properties, which are not independent of each other, are important for the activity of the PCBs.
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