Benzene-initiated oxidative stress: Effects on embryonic signaling pathways

Chemico-biological Interactions
Helen J BadhamLouise M Winn

Abstract

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 chang...Continue Reading

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Citations

Nov 12, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Samantha E Stokes, Louise M Winn
Jan 30, 2014·International Journal of Hygiene and Environmental Health·Julia E HeckBeate Ritz
May 1, 2013·Mutation Research·Angela M MoroSolange C Garcia
Jul 5, 2011·The International Journal of Biochemistry & Cell Biology·Geum-Hwa LeeHan-Jung Chae
Jul 27, 2011·Mutation Research·Anh DuongLuoping Zhang
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Jun 19, 2013·Free Radical Biology & Medicine·Alicia R Timme-LaragyJason M Hansen
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Oct 31, 2016·Asian Pacific Journal of Tropical Medicine·Tahereh FarkhondehFariborz Samini
Oct 23, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Wesley T AbplanalpTimothy E O'Toole
Jan 1, 2020·Antioxidants & Redox Signaling·Jason M HansenCraig Harris
Oct 16, 2019·The Journal of Clinical Endocrinology and Metabolism·Muraly PuttabyatappaVasantha Padmanabhan
Oct 26, 2016·Molecular Medicine Reports·Luca FalzoneMassimo Libra
Apr 8, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Jin HeCheng Peng
Dec 20, 2019·BMC Pharmacology & Toxicology·Angela Maria MoroSolange Cristina Garcia
Jul 25, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Trent H Holmes, Louise M Winn
Oct 13, 2015·Journal of Applied Toxicology : JAT·Nicola A Philbrook, Louise M Winn
Mar 21, 2020·International Journal of Molecular Sciences·Niina BhattaraiAnu Kauppinen
Nov 28, 2020·Environmental Research·Ian W TangVerónica M Vieira
Sep 18, 2020·Toxicology Letters·Colin M NorthStephen D Williams
Jul 10, 2021·Translational Oncology·Wenchao ZhangFernando Rodrigues-Lima

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