| Benzene-initiated oxidative stress: Effects on embryonic signaling pathways. | |
| | |
MedLine Citation:
|
PMID: 19913523 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Approximately 90% of childhood cancers are of unknown etiology; however, it is hypothesized that in utero carcinogen exposure may contribute. Epidemiological studies have correlated parental exposure to benzene with an increased incidence of childhood leukemias. However, mechanisms of benzene-induced carcinogenesis following in utero exposure remain unknown. We hypothesize that in utero exposure to benzene causes alterations in the redox-sensitive signaling pathways involving c-Myb, Pim-1, AKT, ERK-MAPK, p38-MAPK, and NF-kappaB via the production of reactive oxygen species (ROS) as a possible mechanism of in utero-initiated carcinogenesis. Using a CD-1 mouse model we have shown increased oxidative stress in fetal tissue from embryos exposed in utero to benzene by measuring reduced to oxidized glutathione ratios, and increased levels of ROS in male fetuses using flow cytometry and the ROS sensitive fluorescent probe dichlorofluoroscein diacetate (DCFDA). In addition, using Western blotting techniques we observed increased expression of fetal Pim-1, Pim-1 phosphorylation, c-Myb, and phosphorylated p38-MAPK (activated form) and lower protein levels of IkappaBalpha, while phosphorylated ERK-MAPK and AKT protein levels did not change. Interestingly, we found male fetuses more susceptible to benzene-induced oxidative stress, which is in agreement with the literature suggesting that males are more susceptible to benzene toxicity. Further studies evaluating the reason for this gender difference are ongoing. |
| | |
Authors:
|
Helen J Badham; Stephen J Renaud; Joanne Wan; Louise M Winn |
Related Documents
:
|
12840153 - Correction of fatty acid oxidation in carnitine palmitoyl transferase 2-deficient cultu... 22542793 - Involvement of ampk and mapk signaling during the progression of experimental autoimmun... 18434363 - Chicken leptin receptor is functional in activating jak-statpathway in vitro. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-12 |
Journal Detail:
|
Title: Chemico-biological interactions Volume: 184 ISSN: 1872-7786 ISO Abbreviation: Chem. Biol. Interact. Publication Date: 2010 Mar |
Date Detail:
|
Created Date: 2010-03-26 Completed Date: 2010-04-23 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0227276 Medline TA: Chem Biol Interact Country: Ireland |
Other Details:
|
Languages: eng Pagination: 218-21 Citation Subset: IM |
Copyright Information:
|
Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
|
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Benzene / adverse effects* Carcinogens / pharmacology* Embryo, Mammalian / drug effects*, metabolism Female Fetus / drug effects, metabolism Male Mice NF-kappa B / metabolism Oxidative Stress / drug effects* Pregnancy Proto-Oncogene Proteins c-akt / metabolism Proto-Oncogene Proteins c-myb / metabolism Proto-Oncogene Proteins c-pim-1 / metabolism Reactive Oxygen Species / metabolism Signal Transduction / drug effects* p38 Mitogen-Activated Protein Kinases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
FRN 57920//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
|
0/Carcinogens; 0/NF-kappa B; 0/Proto-Oncogene Proteins c-myb; 0/Reactive Oxygen Species; 71-43-2/Benzene; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/Proto-Oncogene Proteins c-pim-1; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Peripherin and ATF3 Genes are Differentially Regulated in Regenerating and Non-Regenerating Primary ...
Next Document: Apoptosis Induction in Human Leukemic Cells by a Novel Protein Bengalin, Isolated from Indian Black ...