Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The toxic equivalent (TEQ) approach is traditionally used in risk evaluation of dioxins. Non-dioxin-like PCBs are not included in this approach and TEQ can therefore underestimate toxicity. In this study, a factorial design and multiple endpoint strategy have been used to evaluate the combined toxicity and possible interactions between the non-dioxin-like PCB 138 and the potent AhR agonists 2,3,7,8-TCDF (TCDF) and 1,2,3,7,8-PeCDD (PCDD). Primary hepatocyte cultures from Atlantic salmon were exposed for 24h and qPCR was employed to create CYP1A dose-response curves and to quantify the transcriptional levels of eight genes (CYP1A, UDPGT, HSP70, GR, GPX, MnSOD, GST and p53). Principal component analysis (PCA) was used to evaluate response similarities between genes. PLS regression was used to model CYP1A and UDPGT responses to the three chemicals. The contour plot examinations of the CYP1A model indicated an antagonism between PCDD and TCDF and in the UDPGT model a possibly synergistic interaction between PCB 138 and PCDD. The results indicate that PCB 138, in combination with TCDF and PCDD, can contribute to the measured CYP1A and UDPGT responses. Using primary cell cultures, multivariate data analysis of qPCR data is shown to be a useful tool in toxicological studies. A multiple endpoints strategy can enhance the quality of risk evaluation of chemical compounds.
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PMID:Factorial design applied for multiple endpoint toxicity evaluation in Atlantic salmon (Salmo salar L.) hepatocytes. 1960 7

PCBs and PCB metabolites have been suggested to cause cytotoxicity by inducing oxidative stress, but the effectiveness of antioxidant intervention after exposure has not been established. Exponentially growing MCF-10A human breast and RWPE-1 human prostate epithelial cells continuously exposed for 5 days to 3 microM PCBs [Aroclor 1254 (Aroclor), PCB153, and the 2-(4-chlorophenyl)-1,4-benzoquinone metabolite of PCB3 (4ClBQ)] were found to exhibit growth inhibition and clonogenic cell killing, with 4ClBQ having the most pronounced effects. These PCBs were also found to increase steady-state levels of intracellular O(2)(*-) and H(2)O(2) (as determined by dihydroethidium, MitoSOX red, and 5-(and 6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate oxidation). These PCBs also caused 1.5- to 5.0-fold increases in MnSOD activity in MCF-10A cells and 2.5- to 5-fold increases in CuZnSOD activity in RWPE-1 cells. Measurement of MitoSOX red oxidation with confocal microscopy coupled with colocalization of MitoTracker green in MCF-10A and RWPE-1 cells supported the hypothesis that PCBs caused increased steady-state levels of O(2)(*-) in mitochondria. Finally, treatment with either N-acetylcysteine (NAC) or the combination of polyethylene glycol (PEG)-conjugated CuZnSOD and PEG-catalase added 1 h after PCBs significantly protected these cells from PCB toxicity. These results support the hypothesis that exposure of exponentially growing human breast and prostate epithelial cells to PCBs causes increased steady-state levels of intracellular O(2)(*-) and H(2)O(2), induction of MnSOD or CuZnSOD activity, and clonogenic cell killing that could be inhibited by a clinically relevant thiol antioxidant, NAC, as well as by catalase and superoxide dismutase after PCB exposure.
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PMID:Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure. 1979 78