Suppression of Depleted Uranium-Induced Neoplastic Transformation of Human Cells by the Phenyl Fatty Acid, Phenyl Acetate: Chemoprevention by Targeting the p21RAS Protein Pathway

Abstract Miller, A. C., Xu, J., Stewart, M. and McClain, D. Suppression of Depleted Uranium-Induced Neoplastic Transformation of Human Cells by the Phenyl Fatty Acid, Phenyl Acetate: Chemoprevention by Targeting the p21RAS Protein Pathway. Depleted uranium is a dense heavy metal used primarily in military applications. Published data from our laboratory have demonstrated that exposure to depleted uranium in vitro can transform immortalized human osteoblast (HOS) cells to the tumorigenic phenotype (associated with aberrant RAS oncogene expression and tumor suppressor protein production). Since depleted uranium is used in military applications, it would therefore be beneficial to identify and test potential antitumor-promoting agents. Chemopreventive interventions that target deregulated signal transduction pathways may be effective strategies to prevent carcinogenesis. Since the RAS protein plays a key role in signal transduction, disruption of its signaling pathway may be particularly effective. The pheny...