Investigating Benzene and Metabolite Mediated Alterations in Nrf2 Signaling in Murine Fetal Liver Cells

Abstract

Leukemia is a cancer of the blood, where the body produces an overabundance of immature white blood cells. It is the most common childhood cancer and possibly originates from chemical exposure during fetal development. Understanding the molecular mechanism and causes of childhood leukemia will help the development of therapeutic and preventative strategies to reduce and treat occurrences of this cancer. Benzene is a non-polar aromatic ring that has been confirmed to cause leukemia in adults. Benzene metabolites can generate free radicals that could potentially be involved in the development of childhood leukemia through in utero exposures. It is found in tobacco smoke, gasoline, industrial solvents and many other substances. Pregnant mothers can be chronically exposed to these substances through daily activities. In order to help determine the mechanism of benzene toxicity, a study was performed to determine the presence of free radicals in the livers of fetal mice at gestation day 14. Fetal liver cell cultures were exposed to varying concentrations of benzene and additional cell cultures were exposed to various concentrations of a benzene metabolite mixture, composed of hydroquinone and benzoquinone. RNA was extracted from these cells and converted into complementary DNA. cDNA was then used in quantitative polymerase chain reactions to analyze a set of genes that are regulated by an antioxidant pathway. This pathway can be activated in response to oxidative stress, and a change in gene expression would indicate the presence of benzene or benzene metabolite toxicity in the liver at gestation day 14.